Mono-allelic germline PALB2 high-risk LOF mutation led to defects in homologous recombination repair (HRR) and caused breast cancer phenotype in our detected PALB2-associated patients, supporting the haploinsufficiency hypothesis for PALB2. Based this hypothesis, we recommended sporadic breast cancers with mono-allelic susceptibility gene mutations to be diagnosed as hereditary breast cancer (HBC), and also recommended their family members to take genetic screen and counseling. Here, PALB2 is linked to breast cancer.