Imiquimod is a topical immune response modifier that binds to Toll-like receptors 7 and 8 and induces α-interferon. We locally applied imiquimod 5% cream (Aldara®) daily for 2 weeks on a PUVA-and retinoid-resistant plaque on the face of a patient with mycosis fungoides. The diagnosis was based on clinical appearance, histology and molecular studies. Most of the disease manifestations showed a clear remission during PUVA therapy combined with low-dose retinoids. However, the plaque on the face was PUVA resistant. Local imiquimod treatment resulted in the complete clearance of the plaque. The patient has now been in complete remission for 12 months.