Objective: Our aim was to review the clinical behavior of human papillomavirus (HPV)-associated digital squamous cell carcinoma (SCC). Specifically, we examined evidence for the tumor's (1) infectious origin and spread, (2) response to therapy, and (3) prognosis and metastatic risk. Design: We reviewed and performed data tabulation of all 51 reported cases in the English-language literature and a case series of 23 cases (21 of them not previously reported). We present 2 of the cases in depth. Setting: We used previously reported cases from MEDLINE and a case series from a single dermatologic operation practice from 1985 to 1999. Results: (1) Of all cases, 10% (7/72) had an antecedent genital dysplasia or carcinoma containing the same HPV subtype as the digital SCC. (2) The rate of recurrence after general surgical therapy was 43% (6/14). After Mohs micrographic surgery the recurrence rate was 13% (2/16) for the cases in the literature, and 26% (6/23) for our case series. (3) Of tumors, 3% (2/72) have been observed to metastasize. Conclusions: (1) This suggests the possibility of genital-digital spread as a mechanism of tumor genesis. (2) HPV-associated digital SCC is more likely to recur after surgical treatment than previously reported. This rate of recurrence greatly exceeds that for cutaneous SCCs in general and may be caused by residual postsurgical HPV. (3) The rate of metastasis, however, appears to be low. (J Am Acad Dermatol 2003;48:385-93.)