Introduction:We report two cases of surgery under general anesthesia during cancer pain management of patients with methadone therapy. Case 1: A 57-year-old woman was started on methadone for pain from right breast cancer with multiple bone metastases, and right mastectomy was performed during the course of chemotherapy. ere was no exacerbation of cancer pain due to methadone withdrawal, although analgesics were used temporarily for wound pain. Case 2: A 76-year-old man was placed on methadone for pain from lung cancer. ere was concern that lower limb paralysis would develop from a compression fracture of the lumbar spine that had occurred during the course of treatment. erefore, decompression and xation surgery was performed. Ketamine was used to control intraoperative pain exacerbation, and fentanyl was used by continuous injection for re-exacerbation of pain after the patient had awakened from anesthesia. Conclusion: Since methadone is available only by mouth in Japan and the equianalgesic ratio between methadone and other opioids has not been established, caution is needed for perioperative pain control while oral methadone cannot be administered. us, pain and palliative care specialists prescribing methadone are expected to play an active role in adequate perioperative pain control.