The abnormal genes that cause “preleukemia” (myelodysplastic syndrome, MDS) are poorly identified. Recently, an extremely robust technology has become available: 500K SNP chips. This glass platform permits us to examine 500,000 sites in the human genome to determine if abnormalities exist in almost every gene in the MDS cells. These chips, therefore, allow us to identify genes that are amplified or deleted or have probable small mutations. Examining a large number of MDS samples and associating the results with clinical data will permit us to develop new diagnostic subcategorization of this heterogeneous group of diseases, provide prognostic indicators for the patients and their physicians, and identify targets of small molecule therapy. Because of its ease and robustness, the 500K SNP chip may become the standard for diagnosis, prognosis, and monitoring progression of MDS, as well as other malignancies.