Background: Regional anesthesia as a primary anesthetic can offer merits over general anesthesia for patients having multiple comorbidities who are at a high risk of perioperative morbidity and mortality. Thoracic paravertebral block (TPVB) and interscalene block (ISB) have been used widely to improve the quality of postoperative analgesia after breast surgery. Objective: There are limited data on the feasibility of combining TPVB-ISB as a sole anesthetic technique for extensive breast surgery with axillary lymph nodes dissection.Case presentation: In this report, the author presented a successful use of a combined TPVB and ISB as a sole anesthetic with conscious sedation in a 52-year-old patient with multiple comorbidities, including heart failure with reduced ejection fraction, who underwent modified radical mastectomy with left axillary lymph nodes dissection. Conclusion: Combining TPVB-ISB can be used as a sole anesthetic for extensive breast surgery in patients with a high risk for general anesthesia.