We discuss imiquimod associated with non-application site mucosal reactions and two of our own clinical cases. In one of our patients, erosive cheilitis developed in a young boy after using topical imiquimod 5% cream for 5 nights weekly on bilateral cheeks, chin, and near vermillion border for molluscum contagiosum. The case is discussed with concerns for imiquimod use in molluscum contagiosum when used near mucosal surfaces.