Numerous clinical studies have shown that anti-EGFR therapies are effective only in a subset of patients with colorectal cancer. Even though mutations in the KRAS gene have been confirmed as negative predictors of the response to EGFR-targeted therapies, not all KRAS wild-type (wt-KRAS) patients will respond to treatment. Recent studies have demonstrated that additionally wild-type BRAF (wt-BRAF) genotype is required for response to panitumumab or cetuximab, suggesting that BRAF genotype criteria should be used together with KRAS genotype for selecting the patients who are about to benefit from the anti-EGFR therapy.