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Background: Non-Hodgkin lymphomas are a heterogeneous group, which involve either B or T lymphocytes. The most used treatment is a chemotherapy regimen, which includes cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone combined with rituximab - a monoclonal antibody specific for CD20 - an antigen expressed on B lymphocyte membrane. Nonmelanoma skin cancers are the most common forms in patients who have lymphomas.Case Presentation: We reported the cases of two Caucasian men affected by non-Hodgkin disease, treated with chemotherapy and rituximab. After treatment, they both presented superficial basal cell carcinoma and we prescribed imiquimod 5 % cream. Unfortunately, the drug was not effective in either patient and the tumors were excised.Conclusions: We speculated about the effect of rituximab on B lymphocytes, on a particular population of T cells and on antigen-presenting dendritic cells that may have determined a lower expression of some surface antigens involved in antigen presentation. These cells are the specific targets of imiquimod to promote skin cancer cells apoptosis. A lack of action by imiquimod on skin cancer after treatment with rituximab is likely due to its transitory inhibitory effects on lymphocytes and Langherans cells. Further studies could be useful to understand the mechanism behind the lack of response. [ABSTRACT FROM AUTHOR]