Suspicion of myelodysplastic syndromes is one of the commonest reasons for bone marrow aspirate in elderly patients presenting with persistent peripheral blood cytopenia of unclear etiology. A peripheral blood assay that accurately rules out myelodysplastic syndromes would have major benefits. The diagnostic accuracy of the intraindividual robust coefficient of variation for neutrophil myeloperoxidase expression measured by flow cytometric analysis in peripheral blood was evaluated in a retrospective derivation study (44 myelodysplastic syndrome cases and 44 controls) and a prospective validation study (68 consecutive patients with suspected myelodysplastic syndromes). Compared with controls, myelodysplastic syndrome cases had higher median robust coefficient of variation values for neutrophil myeloperoxidase expression (40.2% versus 30.9%, P<.001). The area under the receiver operating characteristic curve estimates were 0.94 (95% confidence interval [CI], 0.86-0.97) and 0.87 (95% CI, 0.76-0.94) in the derivation and validation studies, respectively. A robust coefficient of variation lower than 30% ruled out myelodysplastic syndromes with 100% sensitivity (95% CI, 78-100%) and 100% negative predictive value (95% CI, 83%-100%) in the prospective validation study. Neutrophil myeloperoxidase expression measured by flow cytometric analysis in peripheral blood might obviate the need for invasive bone marrow aspirate and biopsy for up to 29% of patients with suspected myelodysplastic syndromes.