Topical imiquimod (IQ) is an effective treatment for genital warts and various malignant tumors of the skin. IQ acts through the Toll-like receptor 7 leading to the production of cytokines and chemokines such as interferons, interleukins, and growth factors. We investigated the composition of the inflammatory cell infiltrate before, during, and after the treatment of 10 superficial cutaneous malignancies (melanoma in situ (n = 4), melanoma metastasis (n = 1), squamous cell carcinoma in situ (n = 4), and basal cell carcinoma (n = 1) with 5% IQ cream. Immunophenotyping revealed in all cases during treatment an increased population of T-lymphocytes positive for CD3, CD4 and CD8, as well as a considerable number of cytotoxic cells (TIA-1+, granzyme B+) and plasmacytoid dendritic cells (CD 123+). These findings further support previous investigations that the antitumor effects of IQ result from an enhanced cytotoxic T-cell mediated immune response and from the recruitment of plasmacytoid dendritic cells to the skin. The population of infiltrative inflammatory cells was similar in all patients irrespective of the type of tumor.