Myelodysplastic syndromes (MDS) comprises a group of acquired hematological disorders which is characterized by a progressive peripheral blood pancytopenia of one or more cell lineages. A high percentage of blast cells in either bone marrow or peripheral blood predisposes for the transformation to acute myeloid leukemia. The clinical presentation with pancytopenia suggest that all cell lineages are affected by MDS. The first experiments with X-linked restriction fragment length polymorphism (RFLP) indicated that MDS is a stem cell disorder since the clonal deletions could be detected in all cell lineages. During the 1st decade several new molecular biological techniques such as polymerase chain reaction, and fluorescent in situ hybridization (FISH) were applied to study molecular aberrations in subpopulations of cells. Molecular aberrations in all subpopulations would indicate that MDS is a stem cell disorder. The clonal studies in MDS are equivocal. Studies involving the expression of chromosomal abnormalities (standard karyotyping and FISH) in different cell lineages suggest that the pluripotent stem cell is not affected in MDS since the lymphoid cells usually do not express the abnormal karyotype. Results obtained by RFLP vary widely. Some studies indicate that the lymphoid lineage is not involved, while other studies find a polyclonal expression of the polymorphic genes in lymphoid cells. One study using PCR demonstrated mutations in the ras-oncogenes in T-cells as well as myeloid cells, suggesting that a common ancestor of myeloid and lymphoid cells is affected by MDS. This review discusses the different experimental approaches carried out to solve the discussion whether MDS is a stem cell disorder.