The currently available targeted therapies for advanced CRC have a limited effect, particularly on the survival of patients carrying tumours with Kras mutation.5 We recently demonstrated that CD44v6-positive CR-CSCs are responsible for metastatic spreading and have a constitutive activation of the PI3K/AKT pathway that appears essential for their survival.33 Here, we demonstrate that CR-CSCs express high levels of HER2, which are associated with a constitutive activation of the PI3K/AKT pathway. This evidence concerns the gene AKT1 and neoplasm.