Monoclonal B-cell lymphocytosis (MBL) is defined as less than 5 × 10(9)/L monoclonal B cells in the blood of otherwise healthy patients and is detected in 5% to 10% of individuals older than 60 years. The bone marrow findings in MBL have hitherto not been systematically described. We have studied the histologic and immunophenotypic findings in paired trephine biopsy specimens and bone marrow aspirates of 26 patients with MBL. Abnormal lymphoid infiltration was detected in trephine biopsy specimens of 20 patients and was demonstrated by flow cytometry of bone marrow in all 26 patients. Three infiltration patterns were discerned: focal interstitial lymphoid infiltration, focal rounded and nonparatrabecular lymphoid aggregates, and discrete diffuse lymphocytosis. Focal interstitial lymphoid infiltration was seen only in patients with chronic lymphocytic leukemia (CLL)-like or atypical CLL-like MBL, whereas the other patterns were not related to a particular MBL immunophenotype. Our results show that most patients with MBL also have bone marrow lymphoid infiltration. The latter should be distinguished from lymphoma infiltration by clinical correlation.