Topical imiquimod is a medication approved for the treatment of external genital and perianal warts, actinic keratosis, and superficial basal cell carcinoma. There have also been reports of its successful use in patients with lentigo maligna melanoma in situ. An 80-year-old female patient was diagnosed with lentigo maligna melanoma in situ which was then surgically removed. After several recurrences, nonsurgical treatment using topical 5% imiquimod was introduced. At 9-month follow-up the skin was completely healed with no evidence of cancer recurrence. In select cases, topical imiquimod seems to be an effective alternative to surgical treatment of melanoma in situ (MIS). Further studies are necessary to assess the successfulness of this treatment method.