In breast, ovarian, pancreatic, and prostate cancers, homologous recombination (HR)–deficiency signatures were more common in tumors with new pathogenic missense mutations in BRCA1/2, PALB2, and RAD51C than in benign missense mutations (66.7% v 35.2%, P = .021). Here, PALB2 is linked to Familial prostate cancer.