Background: Breast cancer is the second most common cancer world-wide following lung cancer. Post-mastectomy pain syndrome (PMPS) is one of the chronic post-surgical pain disorders (CPSP) of neuropathic character; nearly 20–50% of patients may develop PMPS. Stellate ganglion blockade has been performed as a diagnostic, prognostic, or therapeutic intervention for different pain syndromes. Objective: The aim of this study is to evaluate and compare the efficacy and safety of thermal versus super voltage pulsed radiofrequency (RF) application of stellate ganglion in neuropathic PMPS in cancer patients. Study Design: A prospective, double-blind, randomized, and controlled trial. Methods: Eighty patients with PMPS after surgery for breast cancer were recruited from the pain clinic of the National Cancer Institute with pain duration of more than 6 months and less than 2 years, visual analog scale (VAS) ≥ 40 mm, and not responding to oxycodone and pregabalin for at least 4 weeks. The pain had to be of positive neuropathic character, as detected by the grading system for neuropathic pain (GSNP; score of 3 or 4). The patients were allocated into 2 equally sized groups: Group A: Pulsed RF; super voltage pulsed RF was applied with a time of 360 seconds at 42º C, with a pulse width of 20 m/sec and voltage of 60–70 v. Group B: Thermal RF; thermal RF neurolysis was applied with a time of 60 seconds at 80º C, and was then was repeated twice after needle-tip rotation. Stellate ganglion RF therapy was done under fluoroscopy, integrated by ultrasound guidance. The patients were assessed for pain relief by change in VAS score, functional improvement, and the analgesic concomitant medication (oxycodone and pregabalin) consumption prior to block and at 1, 4, 12, and 24 weeks thereafter. The impact of treatment on quality of life (assessed by short-form health survey questionnaire [SF36]) and patient function capacity (assessed by the Eastern Cooperative Oncology Group [ECOG]) were also recorded. Results: The percentage of patients who had successful response was significantly higher in the thermal RF group compared to the pulsed RF group at the first week and first, third, and sixth months, with significant difference in post-mastectomy pain intensity, functional improvement, and less rescue analgesia. There was no significant difference in quality of life or patient functional capacity. Limitations: A longer follow-up period may be needed for the evaluation of RF effect on PMPS. Conclusions: Thermal RF of the stellate ganglion is a safe and successful treatment for PMPS. It appears to be more effective than pulsed RF of the stellate ganglion in this pain syndrome. Key words: Cancer breast, post mastectomy pain syndrome, stellate ganglion block, radiofrequency therapy