Breast cancer can relapse both locally and at distant metastatic sites. The mechanism of local recurrence is unknown, but seems to be due not only to the number of residual cancer cells (inadequate irradiation or surgery), but also to their genetically determined malignant potential. To identify genetic alterations associated with local recurrence risk in breast carcinoma, we analyzed 28 local recurrences and 173 primary breast tumors for the ten most frequently altered genetic regions in breast carcinomas, i.e., loss of heterozygosity on chromosomal arms 1p, 3p, 7q, 11p, 17p, 17q, and 18q, and amplification of the MYC and ERBB2 protooncogenes and of genes in 11q13. Only INT2/FGF3 and CCNDI, located in 11q13, were more frequently amplified in local recurrences than in primary tumors (39% vs. 17%; P < 0.01). Moreover, recurrence-free survival was shorter when the 11q13 region was amplified. These results suggest that one or more genes located in 11q13 play an important role in local relapses of breast cancer.