Although cytomegalovirus has previously been reported in cutaneous lesions of patients infected with the human immunodeficiency virus, these reports are not common despite the prevalence of this infection and the significant pathologic characteristics that it induces in HIV disease. Rare reports of possible epidermal involvement by cytomegalovirus have never been fully documented and have been believed by some to represent epidermal involvement by varicella-zoster and/or herpes simplex infections, with dermal involvement of cytomegalovirus. We present two cases of concurrent epidermal involvement by cytomegalovirus and herpes simplex virus documented by immunohistochemical studies and DNA hybridization studies and correlate this with the distinctive morphologic features seen in these two viral infections on routine staining.