The rationale of rechallenge is based on the possible clonal selection under the pressure of anti-EGFR or anti-VEGF treatment, and requires re-evaluation of RAS/BRAF mutational status in circulating tumor DNA (ctDNA) by liquid biopsy in mCRC patients with acquired resistance to prior chemotherapy plus anti-EGFR. The gene discussed is EGFR; the disease is neoplasm.