In this contention, our recent findings that the Numb–p53 axis maintains the tumor-suppressive barrier of asymmetric division in normal mammary SCs (Tosoni et al., 2015, 2017) provides a reasonable framework to test the possibility that the decreased levels of Numb-1/2 in some BCs is causal to the emergence of CSCs. The gene discussed is NUMB; the disease is neoplasm.