Keratoacanthoma (KA) is a rapidly growing tumour histologically resembling squamous cell carcinoma. Although it may regress spontaneously, KA is routinely treated by excision or radiation therapy. Here we report on the successful therapeutic use of imiquimod for the treatment of KA. Four patients with a one to six week history of facial KA were treated with imiquimod cream 5 % every second day for four to 12 weeks. In each patient, KA fully regressed under topical treatment with imiquimod. In three of the patients, KA had disappeared within four to six weeks. In two patients, disappearance was confirmed histologically. No recurrence occurred during a four- to six-month follow-up-period. Our observations indicate that topical immunostimulation with imiquimod may induce or promote immune defence mechanisms leading to KA regression. Imiquimod might therefore prove to be an effective non-invasive treatment modality for KA that warrants more extensive evaluation by clinical studies.