The aim of our study was to evaluate whether a panel of molecular biomarkers including EGFR GCN, HER-3, IGF-1, B-RAF and PIK3CA prospectively analysed at the start of treatment, might be able to predict colorectal cancer patients clinical outcome during second- third-line treatment with cetuximab in combination with chemotherapy more accurately than RAS status alone. Here, EGFR is linked to colorectal cancer.