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. The gene discussed is PALB2; the disease is Hereditary breast cancer.