Abstract: In vitro evidence indicates that the E6 protein of human papillomavirus (HPV) targets Bak, a proapoptotic protein, expression of which is enhanced in epidermal keratinocytes in response to ultraviolet B radiation. Given this, our aim was to ascertain Bak expression and prevalence of beta-HPV (β-HPV) in cutaneous squamous cell carcinoma (SCC) from sun-exposed sites to test our hypothesis that the virus plays a role in the neoplastic process by suppressing UV-induced apoptosis. This retrospective study included 30 cases of cutaneous SCC and 30 cases of SCC in situ (SCCIS) from sun-exposed sites. Immunohistochemical staining for Bak protein was performed on all, and β-HPV subtyping on 10 randomly selected cases from each group, using a broad-spectrum polymerase chain reaction–reverse hybridization assay. A semiquantitative scoring system for immunohistochemical expression of Bak was used based on the percentage positivity of the cells. Of cases studied, 30 of 30 (100%) of SCCIS and SCC (mean score 4.2 and 4.6, respectively, demonstrated immunopositivity, albeit to varying degrees, with Bak. Of the selected cases studied with reverse hybridization assay, 7 of 10 (70%) of SCCIS and 3 of 10 (30%) of SCC had β-HPV with HPV-5 being the most common subtype detected. Enhanced Bak immunoexpression confirms the presence of UV-induced apoptosis in both in situ as well as invasive epithelial malignancies, although the lack of differences in expression of Bak between both groups studied suggests that its relevance in disease progression is minimal. Expression of Bak in 100% of HPV-containing lesions from sun-exposed sites suggests that the virus does not abrogate UV-induced apoptosis.