BACKGROUND AND DESIGN Human papillomavirus (HPV) is accepted as a factor in the pathogenesis of genital squamous cell carcinomas. The incidences of both HPV infection and squamous cell carcinoma are increased in immunocompromised renal transplantation patients. The purpose of this study was to determine if HPV DNA is present in squamous cell carcinomas of nongenital skin in immunosuppressed patients. Amplification of HPV DNA was performed using the polymerase chain reaction. The sensitivity and specificity of the polymerase chain reaction was assessed on 19 positive and six negative control specimens. Twenty genital squamous cell carcinomas from nonimmunocompromised patients and 28 nongenital squamous cell carcinomas from renal transplantation patients were then analyzed. RESULTS Human papillomavirus DNA was identified in 18 of 19 positive control specimens and zero of six negative control specimens. Human papillomavirus DNA was identified in four of 20 genital squamous cell carcinoma specimens. In comparison, no HPV DNA was identified in 28 nongenital squamous cell carcinomas from immunosuppressed hosts (Fisher's Exact Test, P < .025). CONCLUSIONS These findings support a role for HPV in genital skin cancers and suggest that HPV does not play a role in the increased incidence of squamous cell carcinoma in renal transplantation patients.