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A woman had sexual relations with a soldier who had received smallpox vaccination 5 days earlier. Four days later, she developed a painful annular lesion with central ulceration on her right labium majus. Concerned that she might have acquired vaccinia infection, she attended an urgent care clinic 2 days later, where she received testing and treatment for several sexually transmitted diseases but was not investigated for vaccinia. Over the next few days, more genital lesions appeared, and inguinal lymph node enlargement developed. Specimens obtained by an infectious disease specialist were positive for vaccinia by polymerase chain reaction. At a subsequent visit, the lesions were resolving without specific therapy.