Using functional genomics in a panel of diverse BRCA1/2-isogenic model systems, we identify a robust and penetrant synthetic lethal (SL) interaction between BRCA1/2 mutations and the loss of ADAR1, which operates across a variety of molecular backgrounds, cancer histotypes, and species, and also exists reciprocally, in ADAR1-mutated systems (Figs. 1, 2). Here, ADAR is linked to cancer.