The authors present the case of a 68-year-old male patient with metastatic rectal cancer. A pelvic recurrence resulted in neuropathic pain, radiating down his left leg. The pain was resistant to standard treatments. However, after nearly 3 years of debilitating pain, the patient experienced dramatic relief just hours after an infusion of the antiepidermal growth factor receptor antibody cetuximab. The analgesic effect lasted for 10-12 days and was repeated roughly every 12 days for three and a half years. To test for placebo effect, the patient received (unknown to him) 20% of his usual cetuximab dose and experienced no pain relief. The dramatic analgesic effect was documented in clinical notes, medication lists and in numeric rating scales even while his cancer was in radiological progression. Mitogen-activated protein kinase (MAPK)-signalling is believed to be an important driver of neuropathic pain and therefore, the authors hypothesise a direct inhibition of MAPK-signalling by cetuximab in neuronal or glial cells.