To characterize molecular mechanisms operating in chronic myeloid leukemia (CML) cells with a view toward development of novel therapeutic targets, we analyzed gene-expression profiles of cancer cells from 27 CML patients using a cDNA microarray representing 23,040 human genes. By comparing expression patterns of CML with those of normal cells, we identified 150 genes that were commonly highly up-regulated in CML cells. In addition to 54 genes (34 of them ESTs) whose functions are currently unknown, the up-regulated elements included genes encoding cell-cycle regulators, transcriptional activators, transcriptional factors, and protein kinases as well as proteins already known to be induced in CML, such as some hemoglobins, haptoglobin (HP1), and matrix metalloproteinase 9 (MMP-9), a protein involved in tissue remodeling and tumor invasion. On the other hand, our protocol selected 106 genes, including 13 of unknown function, as being commonly significantly down-regulated in all phases of CML. The results of semiquantitative RT-PCR experiments with 11 representatives of the up-regulated group supported the reliability of our microarray analysis. These data should provide useful information for finding candidate genes whose products might serve as molecular targets for treatment of CML patients.