Periungal and subungual warts are benign epidermal neoplasms caused by human papillomaviruses. They represent a challenge for management because of resistance to treatment. 5-flourouracil is an antimetabolite that interferes with DNA synthesis and inhibits RNA formation. We present a 32-year-old female with subungual and periungual warts of the fingers of both hands and first right toe. She was treated with 5-fluorouracil twice daily under occlusion plus 20 percent urea. After a month she presented with grayish transverse melanonychia along and parallel to the lunula with some maceration of the periungal folds. Nail pigmentation may be a consequence of dermal deposition by systemic drugs and less frequently by topical drugs. In this case melanonychia was induced by the topical application of 5-fluorouracil. The brown-grayish pigmentation, with parallel involvement of the lunula of all the nails treated, presented like that induced by systemically administered cytotoxic drugs.