Lentigo maligna (LM) is an in situ variant of melanoma. Although LM has the potential for invasion, it often has a greatly protracted radial growth phase and may remain indolent for years. The current standard of care is surgical excision, but this often results in substantial morbidity; thus, nonsurgical approaches continue to be investigated. Imiquimod cream 5% is an immunomodulatory agent that previously has been reported to successfully eradicate LM. We evaluated the treatment course of topical imiquimod in 12 patients with LM. Data from patients with biopsy-proven LM were collected retrospectively, reviewed, and summarized. Patients ranged in age from 54 to 83 years. Most patients chose imiquimod cream as their initial form of treatment; however, other patients had a history of LM recurrence after excision or had positive histologic margins at the time of excision. Initial application regimens varied from 2 to 7 times weekly. The average duration of treatment was 15.7 weeks but ranged from 7 to 44 weeks. Results of posttreatment biopsies of the most clinically suspicious areas in 6 patients showed histologic clearance; 2 patients demonstrated single atypical melanocytes and 4 patients demonstrated clinical clearance without histologic confirmation. These findings suggest that imiquimod cream 5% may be an effective alternative treatment for LM.