Abstract Objectives Immunohistochemistry (IHC) is a useful method for mantle cell lymphoma (MCL) detection in the bone marrow (BM). However, recognition of the neoplastic B cells can be challenging, especially when there is low-level disease. Methods We examined BM from 105 patients with MCL. IHC was performed using cyclin D1/CD79a and PAX5/CD5 dual stains, which were compared with single stains that included CD20, CD79a, cyclin D1, and CD5 and with multiparameter flow cytometry (FC). Results Based on the FC data, the overall sensitivity of the dual IHC stains was 95.6%. Both dual IHC stains showed better efficacy for detecting MCL cells compared with the aggregated single stains (P = .012). While three cases were positive by FC analysis but negative for dual staining, four cases showed cells positive for cyclin D1/CD79a and PAX5/CD5 dual staining that were not detected by FC. Two of these latter cases were in patients with minimal or focal disease involvement. Conclusions Cyclin D1/CD79a and PAX5/CD5 dual IHC staining is an efficient procedure for the detection of MCL in the marrow and is particularly helpful in low-level or focal involvement by MCL. This approach can be particularly useful when marrow aspirates are inadequate or unavailable.