Aplastic anemia (AA) and hypoplastic myelodysplastic syndromes (hMDS) are often difficult to distinguish. However, an accurate diagnosis is important because the prognosis and treatment of these diseases may differ. CD34+ hematopoietic progenitors are central to the pathogenesis of both disorders; they are the targets of the autoimmune attack in AA and neoplastic transformation in MDS. The aim of this study was to assess whether bone marrow CD34+ cell numbers could be used in differentiating between AA and hMDS. The percentage of bone marrow CD34+ cells was normal or increased (mean -3.5+0.5%, range 1-7%) in 15 of 35 patients studied, and low (mean -0.13 +/- 0.02%, range 0.02-0.36%) in 20 of 35 patients. All patients with a normal or increased percentage of CD34+ cells were ultimately diagnosed with hMDS based on the detection of clonal cytogenetic abnormalities or progression to refractory anemia with excess blasts/acute myeloid leukemia. All patients with low marrow CD34+ cell numbers met standard clinical criteria for AA and have not demonstrated neoplastic transformation with follow-up. Quantification of marrow CD34+ cells may serve as an important tool for distinguishing between AA and hMDS.