The aim of this study was to review the utility of penile biopsy in genitourinary (GU) medicine clinics, its acceptability and the range of penile dermatoses diagnosed histologically. A retrospective case-notes review of 401 cases attending a dedicated penile dermatoses clinic from 1 June 2001 to 30 November 2007 was carried out. In 115/401 (28.7%) of cases a biopsy was invoked to resolve ambiguities of diagnosis. In 60/401 (15%) of those cases differential diagnosis was resolved, in 26/401 (6.5%) clinically suspected diagnoses were confirmed and in 22/401 (5.5%) clinically unsuspected diagnoses were identified. In 7/401 (1.7%) of cases the biopsy was also the treatment. Targeted penile biopsy has an important role in the diagnosis of penile dermatoses, particularly where there is clinical uncertainty. As a diagnostic tool in GU medicine departments it should be readily available even if not for routine use. There were indications that circumcision may reduce the incidence of penile dermatoses. There was also some indication of a possible ethnic factor in the relative incidences of penile lichen sclerosus and lichen planus in biopsied patients.