A patient is reported in whom treatment-resistant periungual and subungual warts underwent malignant transformation into squamous cell carcinoma. Similar changes were observed in multiple warts of the vulvar, perianal, and intravaginal as well as cervical area. The tumors that developed were in many instances microinvasive but did not metastasize. The remarkable conversion of a common wart into a squamous cell carcinoma further implicates the human papovavirus in oncogenesis. The specific factors accountable for the malignant change remain completely unknown, but the patient's lymphedema praecox, as well as her severe reaction to vaccinia, and her development of a disseminate systemic Mycobacterium scrofulaceum infection suggest that the critical factor may be one of immunity.