The authors studied 48 cases of well-differentiated lymphocytic neoplasms using a panel of monoclonal antibodies applied to frozen sections. Forty-seven tumors expressed monotypic immunoglobulin, one or more B-lineage antigens, and Ia (HLA-DR) antigen. Proliferation centers expressed the T9 antigen and increased numbers of Ki-67-positive cells. One tumor was of T-cell origin, had a cytotoxic/suppressor cell phenotype, and showed anomalous loss of Leu-1 antigen. Immunophenotypic findings were correlated to the clinical presentation and morphologic features of each neoplasm. Sixteen tumors were associated with peripheral lymphocytosis (greater than 4000/cu mm), 13 biopsies were obtained from extranodal sites, 16 tumors had proliferation centers, and 11 neoplasms had plasmacytoid features. The authors found no absolute and few statistically significant immunologic differences between the B-cell tumors according to their clinical presentation or morphologic features. Tumors associated with peripheral lymphocytosis more commonly expressed the Leu-1 antigen (P less than 0.01) and IgD (P less than 0.01) and less frequently were stained by BA-2 (P less than 0.05) and OKT9 (P less than 0.05). Plasmacytoid neoplasms more frequently expressed the Tac (P less than 0.01) and T9 antigens (P less than 0.05), and all expressed kappa light chain (P less than 0.05). Extranodal neoplasms more commonly expressed IgM (P less than 0.01). In contrast to the markedly different clinical presentation and morphologic appearance these tumors may have, the immunologic data suggest that B-cell small lymphocytic neoplasms are relatively homogeneous. For an individual case, immunophenotype does not predict clinical presentation or morphologic features.