Objective: To compare the effects of ultrasound-guided Mammotome rotation cutting and wire-localized surgical resection for non-palpable breast lesion (NPBL), so as to provide the basis for procedure selection in clinical practice. Methods: The clinical data of 362 patients with NPBL undergoing surgical treatment were retrospectively analyzed. Of the patients, 293 cases underwent ultrasound-guided Mammotome procedure (rotation cutting group) and the other 69 cases underwent ultrasound-guided wire-localized surgical resection (open group). The relevant surgical parameters between the two groups were compared. Results: The general data between the two groups of patients showed no significant difference (all P>0.05). Rotation cutting group was superior to open group in variables of operative time, length of incision, and intraoperative blood loss, but the surgical cost in rotation cutting group was significantly higher than that in open group (all P<0.05). The incidence of postoperative complications in rotation cutting group was lower than that in open group, but the difference was not significant (P>0.05). The success rate of surgery in both groups reached 100%. No tumor recurrence occurred in the two groups during followed up for 1 month to 12 months, and evident scars of different sizes were seen in open group, while scars were small or invisible in rotation cutting group. Conclusion: Mammotome rotation cutting for NPBL is safe and effective, and has less bleeding, shorter operative time and favorable cosmetic results, but higher cost compared to wire-localized surgical resection.