Primary acquired melanosis (PAM) with atypical cytological features has nearly a 50% chance of progressing to malignant melanoma. Surgical excision with cryotherapy has been the mainstay of treatment, but topical treatment with mitomycin C (MMC) is an increasingly common alternative treatment. Since PAM is relatively rare and MMC is a new treatment option, publications are limited to case reports and a few small series. Optimum doses, duration and timing of treatment cycles have not been established. Two patients were diagnosed with PAM with atypia and were treated with either primary or adjuvant treatment of 0.02% MMC for approximately 10 days for three cycles, which is the lowest dose protocol published to date for the treatment of PAM. Both patients showed stable partial response and only experienced temporary ocular drug toxicity.