The present invention relates to the prognosis, therapeutic stratification and treatment of colorectal cancer. More in particular, the present invention discloses that significantly increased levels of transmembrane type 1 neuregulin-1 in tumor-associated mesenchymal cells present in a sample of a patient indicate that the patient has a worse prognosis when compared to patients having low levels of transmembrane type 1 neuregulin-1 in tumor-associated mesenchymal cells. Moreover, the present invention relates to the usage of transmembrane type 1 neuregulin-1 expression in tumor-associated mesenchymal cells to predict resistance to HER1 inhibitors during colorectal cancer therapy and/or to predict whether a patient would benefit from a therapy based on the prevention of neuregulin-1 and/or HER3 activity.