Cancer, a disease of the genome, is caused by a combination of germline predisposing variants and acquired somatic mutations. A unified view of heritable and acquired genetic factors will improve our understanding of cancer occurrence and progression. Fanfani and colleagues provide new insight into heritable cancer risk through a computational method that identifies genes and loci that contribute strongly to cancer heritability; many of these loci also harbor somatic drivers. Beyond improving cancer clinical outcomes, these methods will also be valuable across complex disorders by identifying regions responsible for missing heritability.See related article by Fanfani et al., p. 2588.