Eighteen cases of small noncleaved cell lymphoma (SNCL) were studied with a large panel of monoclonal antibodies applied to tissue frozen sections and compared with 18 cases of immunoglobulin-expressing diffuse large cell lymphoma (DLCL). Immunoglobulin expression was seen in all cases of SNCL, with a predominance of cases showing lambda light chain restriction. Expression of mu and delta heavy chains was common, but gamma and alpha chain expression was uncommon. In the cases of SNCL T015, B1, B2, 41H, BA-1, BA-2, Ia, CALLA, and OKT10 were generally expressed, and a large percentage of cells expressed Ki-67. Only rare expression of T05, Leu-8, and Leu-9 was seen, and in no case was reactivity with anti-Tac antibodies observed. In contrast, the immunoglobulin-expressing DLCLs showed the typical predominance of cases of kappa light chain restriction, a lower proportion of cases with mu or delta expression, and a higher proportion of cases with gamma expression. A lower incidence of Leu-8, T05, and Tac expression and a higher incidence of BA-1, CALLA, Ki-67 and OKT10 were seen in the SNCLs as compared with the DLCLs. It is concluded that immunologic studies may be of considerable aid in the differential diagnosis of SNCL and DLCL.