Kaposi's sarcoma (KS) is a vascular neoplasm typically observed in the immunocompromised patient populations, such as acquired immunodeficiency syndrome or transplant patients. KS can appear simultaneously at multiple sites as red to purple, maculo-papular or nodular cutaneous lesions sometimes showing a visceral extension. Sirolimus, an immunosuppressive agent with potent antitumor activity, has been effective in combating post-transplant KS. However, an aggressive regimen of immunosuppression for therapy of severe acute rejection episodes may abolish the antitumor effects of sirolimus. The following is a description of KS development under immunosuppressive therapy with sirolimus, and the successful treatment of KS lesions utilizing the topical application of imiquimod 5% cream, an immune response modifier.