The rash of monkeypox resembles that of smallpox. Prior to the 2022 outbreak, the rash would often begin on the face and spread to other parts of the body, including the palms and soles. Skin lesions on any part of the body were similar and clustered together.

In the 2022 global outbreak, the rash often starts on or near the genitals or in the mouth, is often painful, and may not spread or progress through the typical stages.