Lysozyme, a hitherto myelomonocytic marker, has been previously reported as being raised in the sera of some myeloma patients. This fact, and the sporadical observation of a positive immunohistochemical lysozyme staining seen in some myelomas, prompted us to systematically search for an expression of lysozyme in both neoplastic and reactive plasma cells. A total of 74 paraffin-embedded, formalin-fixed, EDTA-decalcified core biopsies of newly diagnosed cases of plasmacytoma were immunohistochemically investigated for lysozyme expression by a modified avidin-biotin immunoperoxidase technique. The myelomas were subclassified according to their nuclear maturity into poorly differentiated plasmacytoma (PDP) (30 cases), moderately differentiated plasmacytoma (MDP) (24 cases), and well differentiated plasmacytoma (WDP) (20 cases). An unexpected lysozyme positivity was seen in 16/74 cases, and was most prevalent in 10/30 cases of PDP. No correlation has been detected between either lysozyme and kappa or lambda light chain expression, or an abnormal activity of chloroacetate esterase sometimes seen in myeloma. Since lysozyme has not been found in normal plasma cells or reactive plasmacytosis, the expression of this antigen in myeloma represents another example of so-called lineage infidelity, and parallels the previously reported abnormal expression of other myelomonocytic markers in some myelomas and a myeloma cell line. Apart from the unsettled prognostic impact, a facultative lysozyme expression in myeloma must be always considered when applying algorhythmic immunohistological strategies in delineating the histogenesis of haematopoietic or lymphatic malignancies.