A 37-year-old woman presented with an epidermal growth factor-(EGFR)-negative rectum carcinoma with liver metastases. After extensive treatment, consisting of first-line chemotherapy, low anterior resection, isolated liver perfusion, second- and third-line chemotherapy and a pericardiodesis with bleomycin, she was subsequently treated with combination irinotecan and cetuximab therapy. At her last follow-up she had had long-term stable disease for 18 months with clinical benefit. Cetuximab is a monoclonal antibody which targets EGFRR. This exceptional case illustrates that treatment with cetuximab may be of benefit to a patient with EGFR-negative colorectal cancer. The exact mechanism of action and the role ofcetuximab in the treatment of advanced colorectal cancer have still to be determined.