Background: The myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematopoietic stem cell disorders. They are characterized by abnormal bone marrow (BM) differentiation, peripheral blood cytopenias and a risk of transformation into acute myeloid leukemia (AML). The diagnosis of MDS depends on morphological criteria and cytogenetics and is sometimes difficult to make and subjective. Aim: In this study we evaluated the potential of immunophenotyping CD34+ hematopoietic precursors for the diagnosis and classification of myelodysplastic syndromes. Methods: Bone marrow samples of patients with different forms of MDS (51 samples), of healthy controls (15 samples), of patients with cytopenia not due to MDS (disease controls; 39 samples) and of patients with AML (25 samples) were examined. MDS and AML samples were classified according to the WHO criteria. The expression of CD19, CD10, CD133, CD13, CD33, CD117 and CD45 antigens was detected on the CD34+ cells by flow cytometry. Statistical analysis was done with a Mann-Whitney test. Results: The number and immunophenotype of the CD34+ cells in BM of disease controls was similar to that in normal bone marrow. Only the number of CD34+ CD133+ positive cells was low. A high number of CD34+ cells was found in MDS and AML. This number correlated with the percentage of blasts found by cytomorphology. The increase of the CD34+ cell number was accompanied by an increase of the myeloid precursors (CD34+ CD117+) and a decrease of the B cell precursors (CD34+ CD19+). CD117 appeared to be the best marker for myeloid precursors, followed by CD13, especially when the number of blasts was high. A wide range of CD34+ CD133+ and of CD34+ CD33+ positive cells was found in all types of samples. CD133 expression was increased in MDS samples with excess of blasts and in AML. No statistical difference was found between the different groups for the CD33 expression. The myeloid antigen expression on CD34+ cells in refractory anaemia (RA), refractory anaemia with ringed sideroblasts (RARS) and refractory cytopenia with multilineage dysplasia (RCMD) was comparable, although a low positivity for CD133 was found in RARS patients. In MDS with excess of blasts, no statistical differences were found between the myeloid antigen expression on the CD34+ cells of the two subtypes (RAEB-1 and RAEB-2). The phenotype of the CD34+ cells in AML patients with less than 30% blasts (previously RAEB-t) was comparable to that found in AML with multilineage dysplasia and other AML patients. Conclusion: MDS is characterized by a variable number of CD34+ cells in the bone marrow. This number correlated with the percentage of blasts found by cytomorphology. An increase of the number of CD34+ is accompanied by an increase of the myeloid precursors and a decrease of the B lymphoid precursors. In MDS samples with less than 5% blasts the myeloid antigen expression on the blasts was comparable to that in disease controls. In MDS samples with an excess of blasts the phenotype was closer to that of AML.