Amplification is one of the mechanisms by which cellular oncogenes may be altered in their function, possibly leading to neoplastic transformation. The oncogenes c-myc, c- abl , and c-Ki-ras are amplified in several different human neoplasias. The oncogene c-myb, which is specifically expressed and regulated in hematopoietic cells, was found to be amplified in cell lines ML-1, ML-2, and ML-3, which were separately cultured from cells of a patient with acute myelogenous leukemia (AML). A five- to tenfold amplification was correlated with high levels of expression of normal size c-myb messenger RNA and with chromosomal abnormalities in the region 6q22 -24, where the c-myb locus is normally located. Amplification and cytogenetic abnormalities were detected in DNA's from primary and secondary cultures of ML cells, suggesting that they may have contributed to leukemogenesis. The similar AML cell lines HL-60 and ML's contain different amplified oncogenes: c-myc and c-myb, respectively. Alternative activation of structurally and possibly functionally similar oncogenes may distinguish--at the pathogenetic level--phenotypically similar tumors.