Immunophenotyping is a valuable ancillary technique for the differential diagnosis between myelodysplastic syndromes (MDS) with low bone marrow (BM) blast counts and a normal karyotype, and reactive peripheral (PB) cytopenias. Our aim was to search for the most important variables for this purpose. We also analyzed the age variation of BM B-cell precursors (BCP) and its differences in reactive and clonal cytopenias. Immunophenotypic analyzes were performed in BM of 54 patients with MDS (76% with BM blasts <5%) and 35 cases of reactive cytopenias. Healthy allogeneic BM transplantation donors (n = 41) were used as controls. We used a four-color panel of antibodies analyzing 9 granulocytic, 8 monocytic and 6 CD34(+) cell features. Asynchronous shift to the left in maturing granulocytes and increase in CD16(+) monocytes were also found in reactive PB cytopenias, but the most important aberrancies in MDS were seen in myeloid CD34(+) cells. Decrease in BCP, that is a hallmark of MDS, could also be found in reactive cytopenias, especially in patients >55 years. % BM BCP could be calculated by the formula: (-7.97 × log age) + (4.24 × log % CD34 (+) cells) - (0.22 x nr. alterations CD34 (+) cells) + 0.577. Corrected R(2) = 0.467. Analysis of myelomonocytic precursors and CD34(+) cells was satisfactory for the differential diagnosis between reactive PB cytopenias and MDS. The most specific alterations were found in CD34(+) cells. Comparison of the values obtained with those of normal age-matched controls is recommended. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1975931809154663.1044