The diagnosis of myelodysplastic syndromes (MDS) is based on peripheral cytopenias, bone marrow (BM) morphology and karyotyping. This may be difficult in cases with few dysplastic elements in BM and a normal karyotype. We examined the utility of flow cytometric analysis for the differential diagnosis between MDS and non-clonal disorders (NCD) presenting peripheral cytopenias. Quantitative assessment of CD45, CD16, CD13, CD11b, CD10 and CD64 in granulocytes and monocytes, and CD71 and glycophorin A in erythroblasts besides CD34+ cell count was performed in BM of 31 consecutive newly diagnosed patients with MDS, 11 patients with NCD and 11 healthy controls (BM donors). In MDS, the median number of phenotypic abnormalities found was 3 (1-8). The WPSS score showed a correlation with the total number of changes per case (r=0.48; p=0.002). Decreased SSC in promyelocytes correlated with the peripheral neutrophil count (r=-0.46; p=0.007). In NCD, the normal variation of antigen expression along granulocytic and erythroblast maturation was always maintained. In the discriminant analysis, SSC of CD34+ cells, together with that of promyelocytes and metamyelocytes were able to correctly classify 87% of the cases as clonal or non-clonal. Our quantitative approach permitted to detect at least one abnormality in antigen expression in every case of MDS. However, the most important parameters for differential diagnosis with NCD were the analysis of the granularity in immature cells, especially of the granulocytic series.