Cytogenetic changes are common in breast cancer and have also been described in fibroadenomas and fibrocystic disease, but not in histologically normal breast tissue. Cytogenetic analysis was performed on nonmalignant breast tissue from benign breast lumps (n = 8), reduction mammoplasties (n = 31), and grossly nontumorous tissue from cancerous breasts (n = 84), using standard techniques and G-banding. All samples were reviewed histologically. Clonal chromosomal changes were found in three of eight benign breast tumors (38%). Of the reduction mammoplasties, 17 samples contained nonproliferative changes, and three of these (18%) showed a clonal deletion of 3p. No pathology was identified in the other 14 samples, of which one (7%) contained two clonal changes, apparently balanced translocations. Of nontumorous tissues from cancerous breasts, 15 (18%) showed clonal chromosomal abnormalities. Five of these samples were histologically normal. Two clones were identical to those found in the corresponding cancer. In 18 additional samples, single cells were detected with the same change as that seen in clones or single cells in the cancer. Only 4 of these 20 samples contained detectable cancer cells. Clonal abnormalities found in two or more samples included trisomies X, 7, and 20 and monosomies 19 and 18. Clonal changes were not significantly more frequent in proliferative than in nonproliferative lesions. The Icelandic BRCA2 founder mutation, 999del5, was detected in four samples, all histologically normal, two of which had clonal chromosomal abnormalities. In conclusion, clonal chromosomal changes are not infrequent in nonmalignant breast tissue and can be detected even in the absence of histological abnormalities. © 2004 Wiley-Liss, Inc.