Loss of heterozygosity (LOH) from the short arm of chromosome 8 (8p) is common to many human carcinomas, including those of the colon and prostate. It localizes to two discrete regions, 8p21 and 8p22. This suggests the presence of at least two tumor suppressor genes (TSGs) on this chromosome arm. Human breast cancers show consistent 8p deletions in cytogenetic studies, chromosome 8 aneusomy and isochromosome 8q, indicating that the relevant gene(s) may play a role, but the results of molecular analyses of chromosome 8 in breast cancer have been variable. We present here data for 8p LOH in an unselected series of human breast cancers with the use of three CA-repeat markers that showed high rates of LOH in other tumors. All cases were informative for at least one marker, and LOH was seen in 11 of 20 cases (55%). LOH was more frequent for the 8p22 markers D8S254 and D8S133 than for NEFL in 8p21. Regional metastases of the tumors showed allele profiles identical to those of their primaries regardless of whether there was LOH or retention of alleles. One case of microsatellite instability (RER+) was seen. LOH did not correlate with receptor status, ploidy, percentage of cells in S phase, or tumor size: We observed LOH at equal rates in small (< 2 cm) and in larger (> 2 cm) tumors. The data suggest that LOH from 8p is frequent in human breast cancers and that loss of the putative 8p TSG may be an important event in early stage breast cancer.