The clinical and morphologic distinction between small lymphocytic lymphoma (SLL)/ chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) is often challenging and has important prognostic and therapeutic implications. The authors investigated the usefulness of the marker CD23 in discriminating between these processes by flow cytometric immunophenotypic analysis. Consecutive samples of body fluids and hematopoietic tissue from patients with suspected B-cell lymphoproliferative disorders were studied using a panel of antibodies that included pan-B cell markers, CD5, FMC7, and CD23. Specimens from 38 patients with CD5-positive B-cell lymphoproliferative disorders consisting of a monomorphic population of small lymphoid cells were identified. Using standard flow cytometric and/or morphologic criteria, 28 patients were classified as having SLL/CLL and 10 were classified as having MCL. Neoplastic cells from all 28 patients (100%) with SLL/CLL demonstrated CD23 immunoreactivity, whereas neoplastic cells from none of the 10 patients (0%) with MCL demonstrated CD23 immunoreactivity (P < .0001). FMC7 immunoreactivity was observed in one of eight cases of SLL/CLL and in five of five cases of MCL (P = .0047). In conclusion, CD23 is a useful marker for the subclassification of CD5-positive B-cell lymphoproliferative disorders by flow cytometric analysis. FMC7 also may be a useful marker for subclassification.