Interest in the genetics of breast cancer has intensified with the discovery of a breast cancer susceptibility locus, BRCA1, on chromosome 17q. In this paper, we describe updated information on a large breast cancer kindred (K107) that has been extensively studied since 1948. Specifically, we have identified many new cases of cancer in the family and have shown that this family is unlinked to BRCA1 as well as a number of other genes considered as candidates for breast cancer. In a collaborative study between the University of Utah and the Institute of Cancer Research in the United Kingdom, we have collected a set of families with a predisposition to breast and ovarian cancers that have been reliably excluded from linkage to BRCA1 and evaluated their usage in a genomic search for other breast cancer loci. This effort led to the discovery of a second breast cancer locus located on chromosome 13q, BRCA2, which is responsible for the increased incidence of breast cancer in Kindred 107.