Objective To evaluate the value of X-ray guided two-dimensional hook wire localization in preoperative localization of breast microcalcification lesions. Methods The clinical data of 76 breast cancer patients who underwent mastectomy in our hospital from January 2017 to December 2021 were retrospectively analyzed, and they were divided into a test group and a control group according to the different preoperative mammography positioning methods. And the differences in preoperative positioning time, preoperative positioning accuracy, operative time and intraoperative bleeding between the two groups were compared. Results A total of 38 patients underwent modified two-dimensional hookwire positioning before surgery, and the other 38 patients underwent conventional two-dimensional hookwire positioning before surgery. The preoperative positioning time was 10-27 (19.18±4.32) min in the test group and 9-22 (14.95±2.77) min in the control group, with a statistically significant difference between the two groups (P<0.001). The positioning accuracy rate was 92.1% (35/38) in the test group and 68.4% (26/38) in the control group, and the difference between the two groups was statistically significant (P=0.019). The time spent for surgery in the control group (104.37±20.61) min was more than that in the test group (74.68±13.25) min, and the difference was statistically significant (P<0.001). The difference in intraoperative bleeding between the two groups was not statistically significant (P=0.816). Conclusion X-ray guided two-dimensional hookwire localization modification is valuable in preoperative localization of breast microcalcifications lesions and provides an important reference for accurate intraoperative excision of lesions.