How Syphilis Is Diagnosed

Syphilis is a sexually transmitted infection (STI) caused by the bacteria Treponema pallidum. The infection is diagnosed with blood tests that detect proteins, called antibodies, that are produced by the body in response to the infection.

Once you have syphilis, the T. pallidum antibodies will remain in your blood for years. Based on certain test values, the lab may be able to tell if the infection was recent or occurred years ago.

This article looks at what is involved in the diagnosis of syphilis, as well as the various testing options available for at-home or in-office use. It also explains which groups are at high risk of syphilis and when they should seek testing.

syphilis diagnosis
Illustration by Joshua Seong. © Verywell, 2018. 

Self-Checks/At-Home Testing

One of the major drawbacks to STI screening is the discomfort people feel when asking their healthcare provider for a test. Some people may even avoid testing for years until the infection suddenly turns severe and becomes more difficult to treat.

For this reason, some public health officials have endorsed the use of at-home syphilis tests that you can purchase online or at certain drugstores. They are convenient and confidential, allowing you to test yourself in the privacy of your own home.

There are two types of self-tests commonly used for the diagnosis of syphilis:

  • Rapid syphilis test kits: These blood-based tests look similar to a home pregnancy test and can return results in as little as 15 to 20 minutes. While convenient, the tests can be expensive and are vulnerable to user error.
  • Mail-in syphilis tests: These home-based tests require a fingerstick blood draw that is placed on a test card and mailed to a lab for evaluation. The results are usually returned within three to five days via a secure website.

How to Choose an At-Home Test

There is little federal regulation of at-home STI tests. To better ensure accuracy and reliability, only purchase products that bear a Clinical Laboratory Improvement Amendments (CLIA) certification.

Physical Examination

A physical examination may be performed to aid in the diagnosis of syphilis. The exam may be recommended if your medical history and symptoms are strongly suggestive of the disease.

Common signs and symptoms of syphilis include:

  • Painless, open sores (called chancres) on your genitals, lips, or mouth
  • Rash on the body, usually on the palms of your hands or soles of your feet
  • Mild flu-like symptoms such as fever, fatigue, muscle aches, and swollen lymph nodes

While symptoms like these are suggestive of syphilis, only a blood test can definitively diagnose the infection.

Labs and Tests

Syphilis is typically diagnosed with a blood test. Less commonly, syphilis may be detected by looking at a sample of body fluids under the microscope.

A syphilis test performed by a healthcare professional is preferred over an at-home test.

Blood Tests

The preferred method of syphilis testing is a blood test. Two types of tests can detect and confirm syphilis using the same blood sample.

Non-Treponemal Tests

The diagnosis of syphilis starts with a non-treponemal blood test. This includes the venereal disease research laboratory (VDRL) test and the rapid plasma reagin (RPR). Both detect antibodies that are produced by the body in response to damage caused by the infection.

While non-treponemal tests are inexpensive and easy to use, they are prone to false-positive results (meaning that they may say you have syphilis even if you don't). Because of this, a positive result needs to be confirmed with a second, costlier test.

Treponemal Tests

If a non-treponemal test result is positive, one of several treponemal tests would be used to confirm the result. The tests approved for use in the United States include:

  • Chemiluminescence immunoassays (CIA)
  • Enzyme immunoassays (EIA)
  • Fluorescent treponemal antibody absorption (FTA-ABS)
  • T. pallidum particle agglutination assay (TP-PA)

Treponemal tests differ from non-treponemal tests in that they detect antibodies specific to T. pallidum rather than antibodies produced in response to damage caused by T. pallidum.

The results of a treponemal test may either be reactive (meaning T. pallium antibodies have been detected) or non-reactive (meaning that T. pallidum antibodies were not detected).

Window Period for Syphilis

The window period is the time between when you may have been exposed to an infection and when a test can tell if you have the infection. The average syphilis window period is 21 days.

If you get tested during your window period, you might end up with a false-negative result. To be 100% sure about your results, try to wait until after the window period to get tested.

Dark-Field Microscopy

Dark-field microscopy is a direct method of testing less commonly used as it requires highly skilled lab technicians. It is performed by taking a sample of body fluid—either from a chancre or spinal tap—and looking at the fluids under a microscope. The test can also be performed on tissue samples or nasal secretions.

With dark-field microscopy, the technician will be able to see the corkscrew-shaped bacteria under the microscope lens. The test may be useful during late-stage syphilis when antibody levels are low and test results are sometimes inconclusive.

Dark-field microscopy is also useful for testing newborns with congenital syphilis. This is when syphilis is passed from a mother to her unborn child during pregnancy.

Congenital syphilis can be difficult to diagnose because the mother's antibodies will be circulating in the baby's blood for the first 12 to 18 months of life. By examining nasal secretions under the microscope, the lab can confirm whether the baby has T. pallidum or not.

Differential Diagnoses

A differential diagnosis is a process used to distinguish a particular disease (like syphilis) from others with similar features. It may involve additional tests to rule out other explanations for your symptoms.

A differential diagnosis may be especially important with syphilis given that it is sometimes referred to as the "Great Imitator." This is not only because it mimics other diseases but also because the range of symptoms it can mimic changes with the different stages of the infection (known as primary, secondary, and tertiary syphilis).

Among the conditions commonly included in the differential diagnosis of syphilis are:

Stage  Differential Diagnoses
Primary - Chancroid (an STI caused by the bacteria Haemophilus ducreyi)
- Erosive candidiasis (a complication of a genital yeast infection)
- Genital herpes
- Genital squamous cell carcinoma (a form of skin cancer)
- Granuloma inguinale (as STI caused by the bacteria Klebsiella granulomatis)
- Other STIs
Secondary - HIV
- Kawasaki disease (an inflammatory disease affecting blood vessels)
- Mononucleosis (a viral disease caused by the Epstein Barr virus)
- Pityriasis rosea (a common, self-limiting rash)
- Rocky Mountain spotted fever (a potentially fatal tick-borne illness)
- Scarlet fever (an illness caused by the same bacteria as strep throat)
Tertiary - Basal cell carcinoma (a type of skin cancer)
- Brain tumor
- Lupus (an autoimmune disease that can affect different organs)
- Meningitis (inflammation of the membrane and fluids surrounding the brain and spinal cord)
- Mental illness
- Multiple sclerosis (an autoimmune disease affecting the nerve cells of the brain, spinal cords, and eyes)
- Sarcoidosis (an inflammatory disease that causes the formation of granular tissues throughout the body)
- Stroke

Screening Recommendations

Certain groups are more affected by syphilis than others. Because of this, the Centers for Disease Control and Prevention (CDC) and other public health authorities recommend syphilis screening for people at high risk of infection.

At-Risk Group Testing Recommendations
Pregnant people Test at the first prenatal visit, retesting at 28 weeks for those at an increased risk of infection.
Men who have sex with men (MSM) Test at least once annually for sexually active MSM or every 3 to 6 months for those at high risk.
Men who have sex with women (MSW) Consider testing those at high risk of infection.
Women who have sex with women (WSW) Consider testing those at high risk of infection.
Transgender people Consider testing at least once annually.
People with HV Test annually for sexually active people with HIV.

If you think you have been exposed to syphilis, you should never consider the absence of symptoms as a reason not to get tested.


Syphilis is a sexually transmitted infection (STI) caused by a bacteria called Treponema pallidum. The diagnosis typically involves the combination of a non-treponemal and treponemal blood test, both of which detect antibodies produced by the body in response to the infection. A positive result from a non-treponemal test is confirmed with a treponemal test.

Less commonly, syphilis is diagnosed with dark-field microscopy. This is a technique that looks for T. pallidum in body fluids under a microscope. A physical exam may also be involved in the diagnosis.

There are also at-home and mail-in syphilis tests that can be purchased online or at certain drugstores. Although convenient and confidential, they are not as accurate as in-office syphilis tests.

A Word From Verywell

As embarrassing as it can be to ask for a syphilis test, waiting for the results can be downright nerve-wracking. Fortunately, in-office test results are returned relatively quickly once a blood sample is taken.

Even before you get your results, many STI clinics will offer preemptive treatment in the form of a penicillin shot in the buttocks. This is offered in the event you tested during the window period and helps ensure that the clinic doesn't miss the opportunity to treat an infection.

Frequently Asked Questions

  • How soon do syphilis symptoms show up after you become infected?

    Once a syphilis infection is established it takes an average of 21 days before symptoms appear. However, in some cases, it can take as little as 10 days or as many as 90 days before symptoms occur.

  • What is the first sign of syphilis?

    The first symptom of syphilis is usually a single, painless skin ulcer called a chancre that develops at the site of the sexual exposure (such as in the throat or on the genitals or anus). It usually develops three weeks after exposure, although it may not be seen if it develops within the rectum or vagina.

  • What do syphilis lesions look like?

    During primary syphilis, the chancre will usually be round and firm with a red crater at the center. Although painless, the sore will often ooze. During the secondary phase, a rough discolored rash may develop on the palms of the hands and soles of the feet. There may also be open sores or whitish lesions in the mouth,

10 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Ong JJ, Fu H, Smith MK, Tucker JD. Expanding syphilis testing: a scoping review of syphilis testing interventions among key populations. Expert Rev Anti Infect Ther. 2018;16(5):423–32. doi:10.1080/14787210.2018.1463846

  2. Shih SL, Graseck AS, Secura GM, Peipert JF. Screening for STIs at home or in the clinic? Curr Opin Infect Dis. 2011;24(1):78–84. doi:10.1097/QCO.0b013e32834204a8

  3. Centers for Disease Control and Prevention. Syphilis—CDC fact sheet (detailed).

  4. Luo Y, Xie Y, Xiao Y. Laboratory diagnostic tools for syphilis: current status and future prospects. Front Cell Infect Microbiol. 2020;10:574806. doi:10.3389/fcimb.2020.574806

  5. Henao-Martínez AF, Johnson SC. Diagnostic tests for syphilis: new tests and new algorithms. Neurol Clin Pract. 2014;4(2):114-122. doi:10.1212/01.CPJ.0000435752.17621.48

  6. Shah D, Marfatia YS. Serological tests for syphilis. Indian J Sex Transm Dis AIDS. 2019;40(2):186-191. doi:10.4103/ijstd.IJSTD_86_19

  7. Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021MMWR Recomm Rep. 2021;70(4):1-187. doi:10.15585/mmwr.rr7004a1

  8. Klausner JD. The great imitator revealed: syphilis. Top Antivir Med. 2019;27(2):71-74.

  9. Tudor ME, Al Aboud AM, Gossman M. Syphilis. In: StatPearls [Internet]. Treasure Island, FL; StatPearls Publishing; 2022.

  10. Centers for Disease Control and Prevention. Screening recommendations and considerations referenced in treatment guidelines and original sources.

By Elizabeth Boskey, PhD
Elizabeth Boskey, PhD, MPH, CHES, is a social worker, adjunct lecturer, and expert writer in the field of sexually transmitted diseases.