A case of thymoma is presented that was referred for consultation with the differential diagnosis of thymoma and non-Hodgkin's lymphoma. Immunoperoxidase studies performed on fixed, paraffin-embedded sections demonstrated the presence of numerous epithelial cells, supporting the diagnosis of thymoma. However, the pan-B-cell antibody L26 also demonstrated abundant staining, an unexpected finding that may be a potential source of diagnostic confusion. The L26 antibody stained cells with elongate cell processes that interdigitated between and surrounded thymocytes. We pursued this observation by performing immunoperoxidase studies on three thymoma and seven normal thymus specimens using fixed sections. Each thymoma had occasional cells or small clusters of L26-positive cells scattered throughout the neoplasm. In sections of normal thymus, L26-positive cells were also found, almost exclusively in the medullary regions. These cells tended to congregate around Hassall's corpuscles and had elongate cell processes that often surrounded medullary lymphocytes. Occasional small lymphocytes also appeared to be positive for L26. Our results demonstrate that cell populations that express B-cell antigens are consistently found in the thymic medulla and that these cells may be numerous in occasional thymomas. The presence of many L26-positive cells in a mediastinal mass should not dissuade one from making the diagnosis of thymoma if all other findings are consistent with that interpretation.