Male breast cancer is 100 times less frequent than its female counterpart and accounts for less than 1% of all cancers in men. Although men with breast cancer also often have gynecomastia, it is still unknown whether gynecomastia per se predisposes the male breast to malignant disease. We describe the cytogenetic analysis of three gynecomastias and four breast cancers in men. No chromosome abnormalities were detected in two cases of gynecomastia, with no other concomitant breast disease. The third gynecomastia sample, taken from a site where a breast carcinoma had previously been removed, had a t(2;11)(p24;p13) as the sole chromosome change; this is the first time that an abnormal karyotype has been described in gynecomastia. All four cancers had clonal chromosome abnormalities. Several cytogenetically unrelated clones were found in the breast tumor and in a metastasis from case 1. In the carcinoma of case 2, a single abnormal clone was found, characterized by loss of the Y chromosome, monosomy 17, and a deletion of the long arm of chromosome 18. In the carcinoma of case 3, a clone with loss of the Y chromosome as the sole change dominated, accompanied by the gain of an X chromosome in a subclone. In the lymph node metastasis examined from case 4, a single clone carrying trisomies for chromosomes 5 and 16 was detected. Our findings, especially when collated with data on the six karyotypically abnormal breast carcinomas in men described previously, indicate that gain of the X chromosome, gain of chromosome 5, loss of the Y chromosome, loss of chromosome 17, and del(18)(q21) are nonrandom abnormalities in male breast carcinomas.