Although targeted therapy is less toxic than standard chemotherapy, EGFR inhibitors are commonly associated with adverse events, including the inhibition of the MEK/ERK signal pathway, which compromises the epidermis cell differentiation leading to skin lesions.46 Given that HER2 inhibitors generally display minimal dermatological side effects as compared with those induced by EGFR inhibitors,23 as shown by current clinical studies for the treatment of advanced CRC,25 we foresee that triple targeting of HER2, MEK and PI3K may have a superior patient compliance and overall treatment outcome. This evidence concerns the gene ERBB2 and colorectal carcinoma.