Melasma is an acquired cutaneous disorder caused by an overproduction of melanin by the enzyme tyrosinase. Melasma remains a therapeutic challenge and no definitive standard therapy exists. Although hydroquinone (HQ) has emerged as the most common treatment, its popularity has recently waned because of concerns about its potential carcinogenicity and manufacturing challenges. The adverse effects of HQ range from the common irritant contact dermatitis to the less frequent exogenous ochronosis (EO). Previous reports suggest that the risk of leukoderma from HQ treatment is limited to individuals of African descent. Herein, we describe for the first time the development of depigmentation and paradoxical hyperpigmentation in 2 patients with Fitzpatrick skin type III/IV after brief treatment of their melasma with the HQ-containing Nu-Derm and Reverse systems.