Melasma is an acquired symmetric hypermelanosis characterized by irregular light-to gray-brown macules and patches on sun-exposed areas. Many therapeutic agents are available but are unsatisfactory. Recently, it has been demonstrated that lincomycin (LM) and linoleic acid (LA) can inhibit melanogenesis in vitro. Our purpose was to investigate the clinical efficacy of topical application of LM and LA in combination with betamethasone valerate (BV) in melasma patients. Forty-seven Korean female adults with clinically diagnosed melasma were enrolled in a 6-week, double-blind, randomized clinical trial. Patients were treated with one application of the vehicle (group A), 2% LM mixed with 0.05% BV (group B), or 2% LM mixed with 0.05% BV and 2% LA (group C) on the face every night. Determination of efficacy was based on the Melasma Area and Severity Index (MASI) score and objective assessment (no effect, mild, moderate, or excellent) at intervals of 2 weeks until the end of the study at 6 weeks. After 6 weeks, in comparison with the pre-treatment MASI score, the average MASI score of group C decreased to 68.9%, compared with 98% in group A (p<0.05) and 85.4% in group B. There was no statistically significant difference between group A and group B. Seven patients (43.7%) in group C revealed more than moderate improvement in objective assessment, compared with none in group A and two patients (12.5%) in group B. There were no significant side effects. Topical application of linoleic acid is considered to be effective in the treatment of melasma patients.