Tumor suppressor genes APC and MCC were identified recently, and their chromosomal location was ascribed to chromosome 5q21. Mutations in the APC gene give rise to familial adenomatous polyposis and occur in many perhaps even the majority, of sporadic colon cancers. Loss of heterozygosity has been described in other human tumors such as lung and esophageal cancers. Here we show loss of heterozygosity (LOH) in 87 patients with breast cancer for the APC and/or MCC loci using a polymerase chain reaction-LOH assay. LOH affected loci in APC exons 11 and 15 in 9 of 35 (25%) and 4 of 34 (11%) heterozygous patients, respectively. LOH at the MCC exon 10 locus occurred in 7 of 40 (17%) informative samples. These data suggest that allelic deletion of APC and/or MCC is probably involved in the pathogenesis and/or progression of a subset of breast cancers.