A 60-year-old female was seen in the dermatology clinic for evaluation of a nonhealing, tender lesion in the intergluteal cleft. The lesion had been present for more than one month. The patient was heterosexual and her lifetime total number of sexual partners was unknown. Physical examination showed a well-demarcated, red-brown plaque in the superior intergluteal cleft. 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. This lesion did not extend any closer than 2 cm to the anal verge (Figure1). A tangential shave biopsy was also taken in this case, and pathology revealed a non-invasive, moderately differentiated, keratinizing squamous cell carcinoma (Figure (Figures 2,3). The patient was treated with cryotherapy and curettage destruction of the lesion. Additionally, she was referred to gastroenterology for consultation and possible proctologic examination. No additional follow-up has been available yet for this patient.