Neuropathic cancer pain is common, very disabling and difficult to treat. It can be related to tumor invasion of neural structures and neuronal damage by surgery, chemotherapy and radiation therapy. Adjuvant analgesics are often used with opioids to control neuropathic pain in cancer patients. Methadone, a synthetic opioid with multiple mechanisms of action, is gaining increasing importance as an effective agent in the treatment of cancer related neuropathic pain. This case illustrates the challenges of managing severe pain in a patient with head and neck cancer while undergoing anti-tumor treatment. A review of the adjuvant analgesics and opioids, particularly methadone, in the management of neuropathic pain is also included.