Sartore-Bianchi A, et al. - Researchers examined the link between HER2 amplification and response to anti-epidermal growth factor receptor (EGFR) treatment in metastatic colorectal cancer (CRC). They performed molecular screening of HER2 positivity using HERACLES criteria (immunohistochemistry 3+ or 2+ in ≥50% of cells, confirmed by fluorescence in situ hybridization) in patients with KRAS exon 2 wild-type metastatic CRC. Controls were consecutive HER2-negative patients. They found poorer outcome in HER2-positive patients who received treatment with anti-EGFR agents. Since the occurrence of HER2 positivity is not likely to be forecast with main clinicopathological characteristics, testing for HER2 is recommended in all patients with metastatic CRC. Response to anti-EGFR therapy is less likely to be seen among patients with HER2-amplified metastatic CRC.