BACKGROUND: The role of human papillomavirus (HPV) in the induction and maintenance of cervical, anogenital, and some oropharyngeal carcinomas is well recognized, but its role in cutaneous squamous cell carcinoma (SCC) remains to be elucidated. HPV is thought to act as a possible cocarcinogen in the development of SCC. OBJECTIVE: To review the literature assessing the correlation between and possible causation of HPV and cutaneous SCC in immunocompetent and immunocompromised populations. METHODS: We reviewed HPV sampling and detection methods, epidemiologic studies examining HPV carriage in immunocompetent and immunosuppressed individuals, and evidence asserting an association between HPV and cutaneous SCC. RESULTS: Although an abundant body of evidence points toward a link between HPV and cutaneous SCC, many studies indicate otherwise. Recent studies have focused on viral activity in addition to DNA presence. CONCLUSION: The possibility exists that HPV may play a role in the induction but not maintenance of cutaneous SCC.