A case of a cutaneous squamous cell carcinoma (SCC) occurring at the site of a long-standing recurrent HSV infection is described. No deficit of the cell-mediated immunity was recorded. HSV2 was isolated in several viral cultures. HSV DNA was visualized in the SCC by in situ hybridization with biotinylated probes in paraffin-embedded tissue. The samples were negative for HPV2, 5, 16, and 18 probes. A causal relationship between HSV infection and cutaneous SCC is hypothesized.