A 77-year-old woman with a large porokeratosis of Mibelli on the left shin was successfully treated with topical 5% imiquimod cream applied to the entire lesion once daily without occlusion three times a week. A strong inflammatory reaction was achieved in 6 weeks of treatment. The lesion had been present for approximately 6 years and prior treatments included curettage and electrocautery, cryotherapy and topical 5-fluorouracil under occlusion. At the end of treatment with topical 5% imiquimod cream, punch biopsy was negative for porokeratosis. The lesion healed without scarring. At 24-month follow up there had been no sign of clinical recurrence.