Lentigo maligna (LM) is an in situ melanoma which usually occurs in s un-dam aged skin on the head and neck of elderly patients. Depending on the anatomical site and its size treatment of LM can be problematic and usually includes surgic al excision or radiotherapy. Recent reports indicate that topical imiquimodmay b e an effective treatment. However, no data on the underlying immune response in the skin during treatment of LM with topical imiquimod are available so far. We report a 62- year-old caucasian woman with a histologically verified LM which was successfully treated with topical imiquimod 5% cream. Skin biopsy specime ns were obtained before, during (at week 10) and 4 weeks after cessation of topi cal treatment with imiquimod 5% cream. Histological and immunohistochemical ex amination was performed in order to detect residual atypical melanocytes and to characterize the inflammatory infiltrate. A complete clinical and histological c learance of the skin lesion was achieved, with no recurrence up to 9 months afte r the end of treatment. During topical application of imiquimod 5% cream a dep letion of epidermal and dermal CD1a+ dendritic cells was observed. The inflamm atory infiltrate consisted of CD68+ macrophages and mainly of CD3+ T cells w ith a slight predominance of CD8+ T cells. An enhanced expression of granzyme B and TIA- 1 was also noted particularly in the epidermis and near the dermoepi dermal junction. In conclusion, our data indicate that imiquimod 5% cream indu ces a cytotoxic T-cell-mediated immune response in situ which may account fo r the complete destruction of the malignant melanocytes in LM. Further clinical trials and longer follow-up periods on the use of imiquimod for LM are warrant ed. Lentigo maligna (LM) is an in situ melanoma which usually occurs in un-dam aged skin on the head and neck of elderly patients. On the anatomical site and its size treatment of LM can be problematic and usually includes surgic al excision or radiotherapy. Recent reports indicate that topical imiquimodmay be an effective treatment. However, no data on the underlying immune response in the skin during treatment of LM with topical imiquimod are available so far. We report a 62- year-old caucasian woman with a histologically verified LM which was successfully treated with topical imiquimod 5% cream. Skin biopsy specime ns were obtained before, during (week 10) and 4 weeks after cessation of topi cal treatment with imiquimod 5% cream. Histological and immunohistochemical examination was performed in order to detect residual atypical melanocytes and to characterize the inflammatory infiltrate. A complete clinical and histological c learance of the skin lesion was achieved, wi th no recurrence up to 9 months afte r the end of treatment. During topical application of imiquimod 5% cream a depletion of epidermal and dermal CDla + dendritic cells was observed. The inflammtory infiltration consisted of CD68 + macrophages and mainly of CD3 + T cells w † a slight predominance of CD8 + T cells. An enhanced expression of granzyme B and TIA-1 was also preferentially in the epidermis and near the dermoepi- dermal junction. Our conclusion is that our data indicate that imiquimod 5% cream indu ces a cytotoxic T- Cell-mediated immune response in situ which may account fo r the complete destruction of the malignant melanocytes in LM. Further clinical trials and longer follow-up periods on the use of imiquimod for LM are warrant ed.