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CD15 is a useful immunohistochemical marker to identify Reed-Sternberg cells in classical Hodgkin’s lymphoma (HL) and to distinguish it from HD-like neoplasms, but data from the literature concerning its expression in HL are quite variable. Using immunohistochemistry we compared the reactivity of three different anti-CD15 clones (MMA, C3D1 and BY87) and found that anti-CD15 MMA clone is a superior reagent in identifying atypical cells, detecting more numerous cells in 28.2%, and being the only positive marker in 12.8% of cases. We conclude that it is advisable to include this reagent in diagnostic immunohistochemical panels.