Human papillomaviruses (HPVs) are DNA tumour viruses that induce hyperproliferative lesions in cutaneous and mucosal epithelia. The relationship between HPV and non-melanoma skin cancer (NMSC) is important clinically since NMSC is the most common form of malignancy among fair-skinned populations. It is well established that solar ultraviolet (UV) irradiation is the major risk factor for developing NMSC, but a pathogenic role for HPV in the development of NMSC has also been proposed. Recent molecular studies reveal a likely role for HPV infection in skin carcinogenesis as a co-factor in association with UV. This review summarizes the literature describing these data, highlights some of the important findings derived from these studies, and speculates on future perspectives. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.