Bowen disease usually presents as an irregular, asymptomatic, scaly or crusted erythematous plaque that can occur anywhere on the skin. An unusual clinicopathologic variant is described which presents as a well-circumscribed, papillated, exophytic and endophytic, sometimes keratotic lesion. This papillated variant of Bowen disease exhibits keratinocytes with prominent perinuclear halos suggestive of koilocytic change associated with human papillomavirus (HPV) infections. Classic Bowen disease has been associated in previous studies with a variety of HPV types, especially types 16, 18, and 31. Twenty-six patients with papillated Bowen disease were evaluated. The patients included 15 males and 11 females, ranging in age from 33 to 87 years old. Fifty-four percent (14) of the lesions involved the head and neck, 8% (2) involved the trunk, and the remaining 38% (10) involved extremities (including 3 lesions from the hands). Lesions were examined using in situ hybridization with widely screening genomic probes for HPV types 6, 11, 16, 18, 30, 31, 33, 35, 45, 51, and 52. None of the specimens contained HPV DNA from the more common oncogenic HPV types. Given the striking histologic appearance of these lesions, however, this does not exclude HPV infection detectable by more sensitive screening methods such as polymerase chain reaction. Papillated Bowen disease is distinct from other variants, including the verrucous-hyperkeratotic type.