Epithelial membrane antigen (EMA) is generally assumed to be expressed only on epithelial cells. However, EMA was also found on reactive and neoplastic plasma cells, on some non-Hodgkin's lymphomas (particularly cases of T-cell lymphoma and "malignant histiocytosis"), and on Reed-Sternberg cells in cases of lymphocyte-predominant Hodgkin's disease. EMA was also induced on normal blood lymphocytes by exposure to human T-lymphotropic virus type II or phytohaemagglutinin. The specificity of these aberrant reactions was confirmed by the use of three different monoclonal anti-EMA antibodies (E29, HMFG2, and LICR.LON/M8), and by showing that EMA in lymphoid tissue is similar in molecular weight to EMA in human milk. These results indicate that additional anti-epithelial antibodies (eg, anti-cytokeratins) should be used in conjunction with anti-EMA for tumour diagnosis.