The estrogen-receptor locus is a candidate gene for inherited susceptibility to human breast cancer, particularly among families with later onset, primarily estrogen-receptor-positive tumors. For one extended family with eight patients with late-onset disease, one estrogen-receptor haplotype was consistently coinherited with breast cancer, yielding a +1.85 lod score for linkage at zero recombination. Simulation of this pedigree assuming independent inheritance of breast cancer and estrogen-receptor genotypes led to a lod score greater than or equal to 1.85 only once in 2,000 replicates. We suggest testing linkage of this gene to breast cancer in other families with late-onset disease.