Trisomy 12 is the most frequent numerical chromosomal abnormality reported in chronic lymphocytic leukemia (CLL). Its significance in other cancers, however, has not been extensively investigated until recently. Less than 20 cases of polysomy for chromosome 12 have been studied thus far. The most recent data in the literature suggest that gain of chromosome 12 may be a recurrent and sometimes early event in breast carcinogenesis. To test the hypothesis that a subset of breast cancer may be characterized by chromosome 12 trisomy, we conducted a retrospective study of 40 specimens. Of these, ten were stage I, ten were stage II, ten were stage III, and ten were stage IV. Out of the total sample, 12 cases (30%) were found to be presumably trisomic, if a conservative cutoff point of greater than or equal to 15% cells with three signals is adopted. Furthermore, some, but not all, of the 12 cases were found to be likely triploid, when data from a control chromosome 17 probe were taken into account. Thus, our data support the hypothesis that a subset of breast cancer exists which is characterized by an abnormal copy of chromosome 12, in either a diploid or a triploid background.