Flow cytometric immunophenotyping (FCI) aids in the differentiation of chronic lymphocytic leukemia (CLL) from mantle cell lymphoma (MCL); however, overlapping phenotypes may occur. CD11c expression has been reported in up to 90% of CLL cases but has rarely been reported in MCL. Whether CD11c can be used to exclude MCL has not been directly addressed. FCI reports were reviewed for 90 MCL cases (44 patients) and 355 CLL/small lymphocytic lymphoma (SLL) cases (158 patients). MCL cases were confirmed by cyclin D1 immunoreactivity and/or t(11;14) detection by karyotyping or fluorescence in situ hybridization. Cases with typical MCL immunophenotypes did not express CD11c. The 2 MCL cases displaying dim CD11c positivity (2 of 44 patients) expressed other markers not typical of MCL. CD11c was detected in 96 (27.0%) of 355 cases of CLL/SLL representing 53 of 158 patients. CD11c expression is rare in MCL and may aid in differentiation of CD5+ B-cell neoplasms, particularly when small samples limit further ancillary testing.