It is abundantly clear from the contents of this book that our understanding of the inherited aspects of cancer has increased enormously in the past decade. Epidemiological studies (Easton et al., 1995) demonstrate that familial clusters of common cancers could be due to: (1) germline mutations in rare, highly penetrant cancer susceptibility genes, (2) more common, less penetrant mutations, or (3) common environmental factors. It is likely that all of these mechanisms are important. Subsequent to the identification of BRCA1 and BRCA2 (Miki et al., 1994; Wooster et al., 1995), large collaborative studies of families with hereditary breast and ovarian cancer suggest that currently detectable germline mutations in these genes account for approximately 85% of families with six cases of breast cancer but only 41% of those with four to five cases, most families with two ovarian cancer (in addition to breast cancer) cases but 88% (69% due to BRCA1 mutations) with only one ovarian cancer case, while 77% of families with four female cases and one male case of breast cancer are due to BRCA2 and 19% of such families to BRCA1 mutations (Easton et al., 1995; Ford et al., 1998; Thorlacius et al., 1998). Thus a significant proportion of smaller families, particularly those with no cases of ovarian cancer, are likely to be due to polymorphic variants in other genes.