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.