Many cancers, in both children and adults, cluster in families. Collection and statistical analysis of pedigree data suggest that genetic mechanisms play an important role in most cancer types. This is illustrated in colorectal, breast, lung, ovarian, and childhood cancer. Pedigree data are consistent with the hypothesis that cancer is sometimes inherited in an autosomal dominant Mendelian fashion. These rare hereditary cancers might not be different pathogenetically from those arising sporadically. A two-stage model for carcinogenesis provides a framework for the understanding of both forms of cancer. The establishment of registries for familial cancer would be most helpful for cancer risk determinations, surveillance and management programs, identification of new cancer-prone genotypes and etiological family studies.