Background: Classic Kaposi sarcoma usually remains on the skin and has a slow progression; thus, local treatment methods are preferable. Imiquimod is an immunomodulatory agent with antiviral, antitumoural, and antiangiogenic properties that is expedient against Kaposi sarcoma. Objectives: We aimed to clarify whether imiquimod is effective on classic Kaposi sarcoma lesions by comparing imiquimod treatment with cryotherapy, which is the most-used treatment method in our department for this disease. Method: Patients with classic Kaposi sarcoma were included. All lesions of each patient were evaluated and measured by the blinded investigator considering infiltration and surface diameters. Then, lesions were categorized into 2 groups by the other investigator (nonblinded), and imiquimod 5% cream was administered 3 times per week without occlusion in 1 group. Cryotherapy was performed every 3 weeks in the other group. All lesions were reevaluated and measured at the end of 12 weeks by the blinded investigator. Initial and last measurements were compared between the treatment methods. Results: Fifty lesions of 8 patients were included in this study. Imiquimod and cryotherapy were applied to 26 and 24 lesions, respectively. At the end of the study, statistically significant decreases were detected in all scores between weeks 0 and 12 with both treatment methods. Mean percentages of change in scores were not significantly different between the methods. Conclusions: Based on a limited number of patients and lesions treated, we believe imiquimod may be a suitable option to use for the treatment of classic Kaposi sarcoma.