The poly(ADP-ribose) polymerase gene is involved in DNA repair, cell proliferation, differentiation, and malignant transformation. Because dysregulation of PARP expression might lead to genetic instability in human tumors, we examined PARP gene expression and genetic instability in 35 primary human breast carcinomas. Genetic instability was studied by analyzing nine genetic abnormalities among those most frequently observed in breast tumor DNA, including amplification of proto-oncogenes MYC and ERBB2 and chromosome regions 7p, 11q13, and 20q13, and loss of heterozygosity on chromosome arms 1p, 3p, 7p, 7q, and 11p. We found a significant link between strong PARP gene overexpression and low genetic instability (chi2corr. = 5.33; P = 0.012), pointing to a possible involvement of this gene in DNA repair in human breast tumor cells. A trend toward a link between PARP gene overexpression and amplification at 1q41-q44 (the site of the PARP gene) was also observed, suggesting that dysregulation of PARP expression could be due partly to a gene dosage effect.