A patient who had primary acquired melanosis with marked atypia shown on histological studies received topical 0.02% mitomycin C for 2 weeks and 0.04% mitomycin C for an additional 2 weeks. Conjunctival biopsy specimens were obtained to evaluate the efficacy of the treatment. After the first course of mitomycin C administration, some decrease of conjunctival pigmentation was seen, and histological studies disclosed a lower degree of atypia. After the second application of mitomycin C, the pigmentation disappeared except for one small spot that contained only a few typical melanocytes on histological study. The clinical findings did not change during 7 months of follow-up. No adverse reactions to topical mitomycin C occurred except for mild conjunctival hyperemia at the end of the courses of treatment. Administration of topical mitomycin C may be an effective medical treatment for primary acquired melanosis with atypia.