Purpose <p>The aim of this study was to examine the efficacy and safety of methadone for refractory cancer pain caused by pelvic floor lesions.</p> Methods <p>Between April 2016 and September 2023, we retrospectively investigated all cases in which methadone was administered by our Palliative Care Team for refractory cancer pain due to pelvic floor lesions, based on the electronic medical records.</p> Results <p>The extracted cases totaled 36 (21 females), and the age was 55.1 ± 15.1&#xa0;years. The primary sites of malignancy were rectum, colon, and uterine cervix, each of which accounted for nine cases, and others in nine. The causes of refractory pain included pelvic tumors in 36, sacral metastasis/infiltration in 7, and others in 11 (with some overlaps). The prior opioid dosage (oral morphine equivalent) (median, (IQR)) was 168.0 (95.3, 352.5) mg/day. The starting, maximum, and final doses of methadone were 20.0 (10.0, 20.0), 20.0 (13.8, 40.0), and 20.0 (10.0, 37.5) mg/day, respectively, with a treatment duration of 28.0 (16.0, 97.5) days. The pain intensity in NRS on the day before (before) and 7&#xa0;days after (after) the introduction of methadone was 6.0 (5.0, 8.0) and 4.0 (2.0, 5.0), respectively (<i>p</i> &lt; 0.001). The numbers of rescue medications before and after the introduction of methadone were 4.0 (3.0, 5.0) and 3.0 (1.0, 4.0) times/day, respectively (<i>p</i> = 0.0015). Side effects that led to the discontinuation of methadone included nausea and dizziness in one case.</p> Conclusion <p>Methadone is suggested to be an effective and safe treatment option for refractory cancer pain due to pelvic floor lesions.</p>