How Smallpox Is Diagnosed

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Diagnosing smallpox is a matter of recognizing the particular type of lesions it brings about and performing a blood test to detect the presence of the variola virus that causes the disease. However, smallpox has not appeared naturally anywhere in the world since 1977. In fact, most healthcare providers practicing today have never seen an actual case of smallpox so if the disease should show up it's unlikely it would be diagnosed correctly at first.

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Smallpox vs. Chickenpox

Smallpox, like other poxviruses, has lesions that can cover the entire body. Physicians will not likely begin to diagnose smallpox until the lesions become obvious. At that point, healthcare providers will attempt to gain a history of the illness prior to the appearance of the lesions.

To determine the difference between smallpox and chickenpox, the healthcare provider will be looking at the formation of the lesions as the most important sign.

  • Smallpox: Lesions are hard and well-defined. All lesions will develop at the same rate and will be similar in their formation and firmness. Sometimes, the lesions will have a small indentation on their crown, known as an umbilical formation. Smallpox lesions are often preceded up to one to four days by a fever as high as 105 degrees. The lesions will be distributed on the arms and face and appear on palms and soles of the feet.
  • Chickenpox: Lesions are not as well-defined and will be at different stages of development. They are not firm and will be easy to remove. There will not likely be any fever preceding the onset of lesions. The lesions are likely to appear first on the torso rather than the arms and face. They will rarely appear on the palms or soles of the feet.

If you or someone in your family develops lesions that appear to be chickenpox or smallpox, see a healthcare provider.

There is no home treatment for either condition. Smallpox, although extremely unlikely, would be a major medical emergency.

Differential Diagnoses

Other poxviruses can mimic the way smallpox looks but are significantly less lethal than smallpox. Some of these are closely related to the variola virus.


There are several zoonotic (infects animals and humans) versions of orthopoxvirus, the family of virus that includes variola, which is the cause of smallpox. These often look like smallpox and can be similar. Some can be serious.

  • Cowpox affects both cows and humans. Before clinical vaccination (which comes from the Latin word for cow) was widespread, farmers would develop some inoculation of variola through exposure to cowpox.
  • Vaccinia is another virus that affects cattle and is the base virus for the smallpox vaccine.
  • Mpox (formerly known as monkeypox) is the most closely related to smallpox and still naturally infects humans in some African nations. It has a mortality rate of 1 to 10 percent.
  • Camelpox affects camels and can cross over to humans.
  • Buffalopox is closely related to vaccinia and is common in India.

Because smallpox vaccination was stopped in 1980, human populations have lost immunity to not only smallpox but also to many of these zoonotic poxviruses.

Varicella and Herpes-Zoster

Chickenpox is primarily a child illness from the varicella-zoster virus. As mentioned above, chickenpox lesions are less robust than those of smallpox and are very unlikely to appear on the palms or soles of the feet.

Shingles (herpes-zoster) is a secondary infection from the same varicella virus and appears mostly in older adults. Shingles lesions follow major nerve pathways and are nearly always on one side of the body (unilateral). 

Frequently Asked Questions

  • What test is required for the diagnosis of smallpox?

    Smallpox is diagnosed based on a visual examination, history of symptoms, and blood tests that detect the variola virus. However, since smallpox was eradicated in 1980 thanks to a global vaccination program, most doctors practicing today have never seen a case of smallpox. 

  • How can you know if you have smallpox?

    The odds of someone contracting smallpox today are practically nil. The disease has not occurred naturally in the world in almost half a century. Traditionally, smallpox can start as a high fever—up to 105 degrees—for up to four days before skin lesions, or pox, appear on the arms, face, palms, and bottoms of the feet. The lesions are hard, well-defined, and sometimes have a small indentation on their crown. 

  • What is the difference between smallpox and chickenpox?

    Smallpox and chickenpox are both illnesses that present as a rash. Smallpox is caused by the variola virus, while chickenpox is caused by the varicella-zoster virus. Smallpox, which has been eradicated since the late 1970s, appears on the arms, face, hands, and feet, while chickenpox commonly appears on the torso. Chickenpox lesions are not as defined as smallpox lesions.

5 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. History of Smallpox | Smallpox | CDC. Centers for Disease Control and Prevention.

  2. Clinical Disease | Smallpox | CDC. Centers for Disease Control and Prevention.

  3. Evaluating Patients for Smallpox: Acute, Generalized Vesicular or Pustular Rash Illness Protocol | Smallpox | CDC. Centers for Disease Control and Prevention.

  4. Monkeypox. World Health Organization.

  5. Shingles | Clinical Overview - Varicella Vaccine | Herpes Zoster | CDC. Centers for Disease Control and Prevention.

Additional Reading

By Rod Brouhard, EMT-P
Rod Brouhard is an emergency medical technician paramedic (EMT-P), journalist, educator, and advocate for emergency medical service providers and patients.