OBJECTIVES: The aim of the review was to evaluate the efficacy and safety of imiquimod 5% cream compared with vehicle for treating superficial basal cell carcinoma. METHODS: The analysis was performed in accordance with the rules of systematic review, based on the Cochrane Collaboration (Cochrane Reviewer’s Handbook) guidelines and the Health Technology Assessment Agency in Poland (AOTM) recommendations. RESULTS: Two multicenter, vehicle-controlled, randomized clinical trials of high quality were identified according to predefined selection criteria. Treatment with imiquimod 5% cream once a day, 3 times per week resulted in significantly greater complete response rate than vehicle in the period of 6 as well as 12 weeks. Probability of achieving the complete response rate (no histological evidence of superficial basal cell carcinoma in the excised post–treatment target tumor tissue) was significantly greater for imiquimod 5% cream than vehicle and amounted to 18.2 (95% CI: 4.19; 84.84) and 146.14 (95% CI: 69.3; 323.75) respectively at 12 and 6 weeks after treatment. The incidence of adverse events during the treatment period such as application site reaction including itching, pain and tenderness at the target tumor site and local skin reaction such as erythema, scabbing, were more frequently recorded in the group of subjects who received imiquimod 5% cream in comparison with the vehicle group. CONCLUSIONS: Imiquimod 5% cream appears to be effective in the treatment of superficial basal cell carcinoma. A 3 times a week dosing demonstrates high efficacy results with acceptable safety profile, during the 6 as well as 12-week period.