Objective: To explore the clinical effect of minimally invasive breast circumcision in patients with palpable negative breast lesions. Methods: A total of 251 patients with palpation negative breast lesions were enrolled in this study, who were treated in our hospital from December 2017 to March 2020. All patients were treated with minimally invasive circumcision of the breast. The pathological results, excellent rate of breast shape, operation related indicators, complications, and life quality before and after the operation were analyzed. Results: Among 251 patients, there were 244 patients with benign lesions and 7 patients with malignant lesions. And there were 117 patients with excellent appearance of breast shape, 125 patients with good appearance, yielding an excellent-to-good rate of 96.41% for breast shape. And the operation time was (20.85±4.26) min, the intraoperative hemorrhage was (4.05±1.03) mL, the incision length was (3.29±0.41) mm, the hospitalization time was (2.06±0.37) d; the incidence of complications was 4.78% (12/251). The postoperative scores of family role, social role, language, personality, energy and emotion were 11.25±1.34, 11.27±1.28, 14.14±1.42, 11.37±1.27, 11.03±1.28, and 13.01±1.23, respectively, which were significantly higher than those before the operation (P<0.05). Conclusion: The minimally invasive breast circumcision is effective in the treatment of patients with palpation negative breast lesions, which can effectively maintain the breast shape and improve the life quality and is worthy of further clinical research and application.