The common loss region on the short arm of chromosome 3 (3p) in human breast tumors harbors two members of the c-erbA receptor gene family, c-erbA2 and c-erbA-beta, both of which recognize a BamHI polymorphism in human genomic DNA. Analysis of lymphocyte DNAs from 50 normal individuals and lymphocyte DNAs from 50 normal individuals and lymphocyte and tumor DNAs from 116 breast cancer patients revealed identical genotypes (a/a, b/b or a/b) for both probes. Furthermore, deletion of the same allele (a/- or -/b) of c-erbA2 and c-erbA-beta was detected in 25% of the 66 breast tumors from patients with constitutionally heterozygous genotypes for both genes. No sequence homology was detected between the c-erbA2 and c-erbA-beta genes, suggesting a physical linkage between these two genes. Digestion of the genomic DNA with combinations of restriction enzymes and hybridization with c-erbA2, which is a genomic fragment, and c-erbA-beta, which is a cDNA clone, provide evidence that c-erbA2 and a region of the c-erbA-beta gene are physically contiguous on the short arm of chromosome 3 and are separated by no more than 1.8 kb of DNA sequences.