Clinical studies have suggested that the epidermal growth factor receptor (EGFR)-inhibiting antibody cetuximab may have better effect in the third-line treatment of metastatic colorectal cancer, after failure of standard chemotherapy including oxaliplatin, compared to using it up-front in the first line. The reason behind this suggestion is unclear.The effect of cetuximab on cell growth was investigated in five isogenic colon cancer cell lines with increasing level of acquired oxaliplatin resistance. The expression of EGFR and the activity of down-stream signalling molecules were measured by western blot analyses.A marked increase in sensitivity to cetuximab, accompanied by an up-regulation of EGFR, was observed in the oxaliplatin-resistant cell lines.The connection between oxaliplatin resistance and cetuximab sensitivity has not been previously reported in the literature. Such a connection could be of clinical importance and constitutes a substantial an argument for saving cetuximab until later treatment lines, when the tumours have become chemotherapy resistant.