A 53 year old female patient developed a keratoacanthoma, present on the left side of her nose for two months. After repeated unsuccessful trials with cryotherapy, she was treated with intralesional injection of methotrexate performed twice with a weekly internal. This led to complete resolution within 5 weeks. Although controlled studies on the effect of methotrexate in keratoacanthoma are not available, the rapid regression and the good cosmetic result suggest that this therapy may play a beneficial role in treating these lesions especially in problem locations.