A 66-year-old female was seen in the dermatology clinic for evaluation of an "irritated nevus" of the intergluteal cleft. The lesion had been present for 6 years. The patient was heterosexual with a lifetime total of 5 to 10 sexual partners. She denied a history of any sexually transmitted infections. Physical examination revealed a brown, verrucous nodule and several smaller verrucous papules in an immediate perianal distribution; these lesions were clinically consistent with condyloma acuminata. In addition, a large red-brown plaque was noted in the superior intergluteal cleft, extending to the anal verge (Figure (Figure1). A tangential skin shave biopsy demonstrated full thickness keratinocyte dysplasia, with marked nuclear atypia and numerous mitotic figures, consistent with a diagnosis of intraepithelial squamous cell carcinoma (Figures (Figures 2,3). Serologic testing for viral hepatitis and syphilis was negative. Fluorescent in-situ hybridization (FISH) for high- and low-risk HPV was performed on formalin fixed, paraffin embedded tissue. It was negative for both categories of HPV. The patient was referred for colorectal surgery and the lesions were excised with wide margins. Severe dysplasia within the perianal area recurred 1 year later and she was treated with topical imiquimod. Further follow-up is planned.