Cutaneous cytomegalovirus (CMV) infection has been observed in a variety of nonspecific skin lesions. Because of this fact, its diagnosis is rare and frequently accidental. The presence of the virus has also been observed in apparently normal skin, from both a clinical and histological point of view. In this context, skin biopsy and immunohistochemistry are often the first means of diagnosis of systemic CMV infection. In 180 skin biopsies carried out on HIV patients in the Infectious and Parasitic Diseases Unit, typical histopathological findings of CMV infection in a nonspecific skin lesion were observed in only one patient. Although the patient showed no extracutaneous manifestations at this time, she died soon after this diagnosis. Because of this fact, we review the literature and discuss the difficulties and implications of the diagnosis of cutaneous CMV infection in AIDS patients.