B-cell non-Hodgkin's lymphomas with a marked preponderance of reactive T cells, so-called T-cell rich B-cell lymphomas (TCRBCLs), can be morphologically confused with Hodgkin's disease (HD). To establish helpful distinguishing features in paraffin sections, 10 cases of L26-positive, CD15-negative HD and 10 cases of TCRBCL were compared; 4 cases of HD had morphologic features of the nodular lymphocyte predominant (LP) type. Nine of 10 cases of HD contained fewer than 20 mitoses/20 high power fields (hpf) and only 1 had pericapsular involvement. In contrast, 9 of 10 TCRBCL had greater than 20 mitoses/20 hpf and 7 had perinodal infiltration. HDLP was easily distinguished from TCRBCL by the expanded dendritic meshworks outlining the L & H nodules and the high content of CD57-positive lymphocytes. The remaining 6 cases of non-LP L26-positive HD had a relatively distinctive immunostaining pattern, with absence of CD45 and discordant reactivity for L26 and Ki-B5 in Reed-Sternberg cells and variants. Only 3 cases of TCRBCL had a similar CD45 and L26/Ki-B5 immunostaining pattern, and these could be distinguished by demonstrable cytoplasmic light-chain restriction. These results show that evaluation of the mitotic count, pericapsular involvement, and immunohistochemical staining patterns for Ki-M4p, CD57, L26/Ki-B5, and CD45 can help to discriminate TCRBCL from L26-positive HD when only fixed material is available.