Objective: To assess the effectiveness and safety of a 24-week application of tretinoin 0.025% cream, with an alternate-day regimen, in achieving control of VLS signs and symptoms. Methods: 17 patients affected with VLS were included. The main efficacy parameters were the response rate, as defined by protocol parameters, the rate of patients achieving an improvement from baseline of >= 75% in the subjective and objective scores, and the mean reduction in subjective and objective scores throughout the treatment. The safety of the treatment was also assessed. Results: By the end of the 24-week treatment, 12 patients (70.6%) experienced a response; 35.3% and 17.6% of patients achieved an improvement of at least 75% in subjective and objective scores, respectively. Mean scores of itching, leukoderma (pallor) and hyperkeratosis decreased significantly in the study patients, and none presented itching-related excoriations. Erythema increased compared with baseline. Six patients (35.29%) experienced some side effects related to tretinoin, mainly mild erythema and burning. None of the subjects discontinued the treatment because of side effects. Conclusions: Tretinoin 0.025% cream applied for 24 weeks may represent a useful alternative option to corticosteroids in the treatment of active VLS, acting particularly on hyperkeratosis and pallor.