Breast cancer has been recognized for over 100 years as having a familial component.1 More recently, a number of epidemiological investigations have attempted to quantify the risks of breast cancer associated with a positive family history. Attempts have also been made to examine whether the pattern of related individuals with breast cancer are consistent with the effects of a single gene of large effect, shared environmental effects, many genes acting in an additive manner or, more likely, a combination of two or more of these effects. In addition to this statistical and observational evidence for the role of genes in the development of breast cancer, a number of specific genes have been identified as playing a role. Perhaps the most notable of these genes are BRCA1 and BRCA2, which were identified through genetic linkage studies and localized to the long arms of chromosomes 17 and 13, respectively.2,3 Because BRCA1 and BRCA2 have been extensively studied, they are the subjects of a separate chapter (Chapter 19) in this book. However, the BRCA1 and BRCA2 genes account for less than half of all familial breast cancer.4