Background: The brachial plexus nerves originate from the cervical (C5-C8) and first thoracic (T1) spinal nerves, and innervate muscles and skin of the chest, shoulder, arm and hand. Brachial plexus injuries can occur as a result of shoulder trauma and inflammation. Malignant tumors can also cause neoplastic brachial plexopathy (NBP), and refractory neuropathic pain is the most common symptom of NBP. Methadone is a synthetic opioid with high efficacy as an opioid-receptor agonist, and its inhibitory effects on N-methyl-D-aspartate (NMDA) may play a role in pain relief. However, there is a need to examine if oral methadone exhibits safety and efficacy against neuropathic pain due to NBP. Case Presentations: NBP was diagnosed in 3 cases without brain or cervical spine metastasis. The clinical features of these patients were analyzed retrospectively. None of the cases had an indication for surgery because of advanced cancer and all had received radiation therapy that had an insufficient effect, prior to methadone treatment. All 3 patients had nociceptive and neuropathic pain. Methadone for refractory pain was initiated using the stop-and-go method. NRS pain scores decreased in all cases and there were no severe side effects. Discussion: For the purpose of pain relief, patients with NBP may receive surgery, radiation therapy and nerve block, but these are not always effective. Methadone was recently shown to be superior to fentanyl in treating neuropathic pain in patients with head-and-neck cancer in a RCT, and our findings suggest that methadone may also be effective for patients with NBP. Conclusion: More studies are necessary, but results in 3 cases suggest that oral methadone may be a safe analgesic agent for patients with neuropathic pain due to NBP.