We evaluated the role of flow cytometric immunophenotyping (FCI) in the assessment of bone marrow (BM) specimens in 104 patients with mantle cell lymphoma (MCL) following treatment with aggressive combination chemotherapy. Of the patients, 77 had no morphologic or FCI evidence of MCL, 13 had morphologic and FCI evidence of MCL, and 14 patients were morphologically negative but FCI showed CD5+ clonal B-cells (M-/FCI+). Retrospective cyclin D1 immunostaining was positive in 3 of 12 M-/FCI+ cases. Clinical staging and follow-up showed that 4 of 12 patients had concurrent extramedullary involvement by MCL, 5 patients subsequently became M+ for MCL in BM (within 2-24 months), and 3 patients had no recurrent MCL on follow-up. We conclude that FCI is more sensitive than morphologic examination of BM at the time of restaging in patients with MCL and that positivity by only FCI in BM often correlates with concurrent disease or subsequent relapse.