There are about 20 types of human papillomaviruses (HPVs) which are generally believed to be confined to the anogenital tract. HPV 16 is the most common of these. Four squamous cell carcinomas of the finger from three individuals were analyzed for the presence of HPV DNA by Pst 1 restriction enzyme digest and Southern blotting. Under high stringency conditions, all were positive for HPV 16. The DNA from each patient was digested with a panel of restriction enzymes so that integration of HPV into the genome could be evaluated. Three of three samples contained high molecular weight oligomeric circular DNA arranged as catanates. None showed integration. To determine if the HPV was transcriptionally active, RNA was isolated, reverse transcribed, and amplified using primers that amplified the unspliced E6 transcript and the E6I and E6II spliced transcripts. All of the patient biopsies assayed expressed the unspliced E6 transcript and the spliced E6I transcript with the E6I transcript being the most abundant. The E6II transcript was not detected in any of the samples. These findings indicate that HPV plays a role in the development of squamous cell carcinoma of the finger and the role of the malignant genital HPV needs to be carefully looked at in areas outside the genital region. It also suggests that the natural history of HPV in areas outside the cervix may not be identical to that of HPV in the anogenital region.