Chromosome painting was used to determine the copy number-and identity of virtually all the chromosomes in three breast cancer cell lines, T-47D, MDA-MB-361, and ZR-75-1. The karyotypes of all three cell lines were very complex, and were consistent with the monosomic pattern of evolution suggested by Dutrillaux, in which nonreciprocal translocations cause an initial reduction in chromosome number, followed by duplication of the entire genome and further chromosome loss. Twenty distinct abnormal chromosomes were identified in T-47D, seven of which were present as two copies. MDA-MB-361 had 27 abnormal chromosomes, each as a single copy. Thirteen abnormal chromosomes in ZR-75-1 occur-red singly, two were paired, and one was present as three copies. Most of the abet-rant chromosomes were nonreciprocal translocations, although deletions, duplications, isochromosomes, and amplifications (HSR of Iq) were also found. Chromosome arms present in abnormal chromosomes in all three lines were 1q, 6p, 7p, 8p, 8q, 10q, 11p, 11q, 12p, 13q, 14q, 15q, 16p, 16q, 17q, and 20q, The only chromosome arms present in four or more copies in all three lines were 8q and proximal 12p, while Ip, 17p, and bands 11q 12-13 were the only chromosome regions consistently reduced to two copies. The most striking feature common to all three lines was a translocation breakpoint on the shore arm of chromosome 8 at 8p12. (C) 1997 Wiley-Liss, Inc.