The aim of this study was to explore the mechanism underlying the blast crisis of chronic myeloid leukemia. Analysis of gene expression profiles of chronic myeloid leukemia patients in chronic phase and blast crisis were analyzed by using cDNA microarray representing 4096 genes for finding the differential expression genes. The results indicated that 74 differential expression genes were identified in at least 3 gene chips in blast crisis compared with chronic phase, among them 52 genes were down-regulated and 22 genes were up-regulated in blast crisis. The differential expression genes were involved in these genes including genes related to cell structure/mobility, signal transduction, transcription factor, related immunity, metabolism, cell cycle, oncogene/anti-oncogene, cell receptor, protein translation/synthesis and some unknown functions. It is concluded that the blast crisis of CML is resulted from abnormality and interaction of multigene, among them functional abnormal genes related to signal transduction, cell cycle, cell differentiation and immunity may be the critical genes for chronic myeloid leukemia blast crisis.