In contrast to squamous cell carcinoma of the penis, scrotal carcinoma has historically been associated with exposure to environmental or industrial carcinogens and has only rarely been correlated with human papillomavirus. We report on a patient with squamous cell carcinoma of the scrotum in which human papillomavirus type 16 was integrated into the tumor cell genome, suggesting a causal role of human papillomavirus in the development of squamous cell carcinoma of the scrotum. Other unique features of our case include the presence of Darier's disease, an uncommon genodermatosis, and treatment with oral retinoids, which have prophylactic value in the prevention of cutaneous malignancies. © 1995 American Urological Association, Inc.