Diagnosis of myelodysplastic syndromes (MDS) could be difficult. We explored the usefulness of the enumeration of maturing B-lineage precursors (hematogones) by multiparameter flow cytometric analysis in the diagnosis of MDS in bone marrow (BM) specimens. We evaluated 111 MDS, 120 non-MDS (most with cytopenias; control group 1), and 41 noncytopenic lymphoma staging BM (control group 2) specimens. The percentage of total hematogones was significantly lower in MDS (median, 0%; mean, 0.10%) compared with non-MDS (control group 1, median, 0.38%, and mean, 0.91%; control group 2, median, 0.38%, and mean, 0.60%; P < .0001), as was the percentage of the most immature (stage I) hematogones. Thus, hematogone enumeration may serve as a biomarker to aid in the diagnosis of MDS. Interestingly, the percentage of hematogones was not significantly different between MDS subgroups or patients with MDS with and without chromosomal abnormalities, implying that a defect in maturing B-cell precursors may be an early event in the pathogenesis of MDS.