Myelodysplastic syndromes (MDSs) are a group of clonal hematological malignancies, characterized by hyperproliferative but ineffective hematopoiesis. Cytogenetic abnormalities are identified in 30 to 70% of de novo MDS. We present the case of a 54 year-old male patient with multiple chromosomal aberrations revealed during MDS evolution. Cytogenetic investigation has been performed by classical chromosome studies (GTG banding) and standard FISH techniques. Complex numerical and structural anomalies were identified in bone marrow cells. Modal chromosome number was 51 (48-51). Hyperdiploidy resulted from trisomy 1, 8, 14, 21 and the presence of supernumerary marker similar to C group. Structural rearrangements of autosomes 1 and 19 were observed. FISH with chromosome 14 painting and centromeric probe for chromosome 8 confirmed the classical cytogenetic findings. Quantitative alterations of chromosome 8 (either total or partial trisomy 8) are commonly found in MDS, as well as trisomy 14. Also, trisomy 21 is the second most frequent acquired trisomy in adult MDS. In our case, frequently described trisomies associate to structural aberrations that necessitate further studies for a detailed characterization. The impact of these complex genomic alterations on disease evolution has been unfavorable. The patient progressed towards acute myeloid leukemia and died of infectious complication. Acknowledgements: National Program for Research of Excelence CEEX MIII, Project no. 15/2006.