Cytogenetic analysis of short-term cultures from 15 cases of benign proliferative breast disease (PBD), 10 diffuse PBD and 5 papillomas, and 15 fibroadenomas of the breast revealed clonal chromosome abnormalities in 7 diffuse PBD lesions, 4 papillomas and 5 fibroadenomas. The remaining 14 cases had a normal female chromosome complement. Cytogenetically unrelated abnormal clones were seen in 4 fibroadenomas and 2 PBDs. A single abnormal clone was found in 9 PBDs and 1 fibroadenoma. Three clonal abnormalities were seen as recurrent changes in 6 cases, namely interstitial deletions of 3p with 3p 12-14 as the minimally common deleted segment (in 1 papilloma, 1 diffuse PBD with atypia and 1 mixed-pattern lesion with both papilloma and atypical diffuse PBD features), r(9)(p24q34) (in 1 diffuse PBD and 1 fibroadenoma), and del(1)(q12)(again in 1 diffuse PBD and 1 fibroadenoma). Intriguingly, 6 of the 16 abnormal cases had chromosome changes that have been seen repeatedly as primary abnormalities in breast carcinomas: der(16)t(1;16)(q10;p10), del(3)(p12p14), and del(1)(q12). We conclude that some of the chromosome anomalies frequently found in breast carcinomas are also present in PBD and fibroadenomas. These aberrations may be accepted as early, neoplasia-relevant mutations. However, they do not seem to be sufficient by themselves to unleash a malignant process.