Intraepithelial penile carcinoma (IPC) is an in situ carcinoma of the penis, which can be difficult to diagnose. Current treatments include excisional surgery, Mohs' micrographic surgery, cryotherapy, carbon dioxide laser therapy and topical 5-fluorouracil. We report two cases of men with 12-18 month histories of IPC (Bowen's disease, squamous cell carcinoma in situ) that were previously unsuccessfully treated with antifungals and antibiotics. Treatment with imiquimod 5% cream for 8-10 weeks was effective in both cases with no clinical evidence of relapse at 4 and 6 months. Both patients experienced adverse effects, resulting in temporary discontinuation of treatment.