Background: CD23 and FMC7 are normal B-cell antigens utilized during diagnostic immunophenotyping of suspected lymphoproliferative disorders. However, the diagnostic utility of coexistent antigenic expression patterns with simultaneous two-color staining and flow cytometric analysis has not been studied extensively. Methods: Using multiparameter flow cytometry, we evaluated the expression pattern of FMC7 and CD23 in 218 cases of B-cell lymphoma from blood and bone marrow specimens. Results: The CD23(+)/FMC7(-) pattern was the most common pattern in patients with chronic lymphocytic leukemia and related variants. The widest variation of patterns was found in patients with follicular cell lymphoma, large cell lymphoma, and Waldenström's macroglobulinemia, a lymphoplasmacytoid disorder, although most cases expressed the CD23-/FMC7(+) pattern. The CD23 and FMC7 antigen, along with the CD5 coexpression pattern, provides critical adjunctive data. These data allow accurate classification of the majority of cases, thereby providing a key aspect of a reliable diagnostic algorithm. The CD23 and FMC7 antigen expression pattern, along with selected other antigens, was predictive of subtypes in >95% of lymphoproliferative cases and narrowed the differential diagnosis in the remaining cases. Conclusion: The flow cytometric CD23/FMC7 expression pattern achieved by multicolor immunophenotyping facilitates accurate and reproducible classification of B-cell lymphomas and has diagnostic utility. Cytometry (Clin. Cytometry) 50:1–7, 2002. © 2002 Wiley-Liss, Inc.