HYPOTHESIS: Sonographic hematoma-guided (SHG) lumpectomy achieves better margin clearance with a smaller volume of resection compared with wire-localized (WL) lumpectomy. DESIGN: Retrospective study. SETTING: University Comprehensive Breast Center. PATIENTS: Consecutive patients treated over 6 months at the breast center with stereotactic biopsy-proven cancers that were not visualized on ultrasonography. The SHG and WL techniques were compared. MAIN OUTCOME MEASURES: The matching variables were age, mammographic abnormality, tumor size and type, and lymph node status. The outcome variables were the closest margin of resection, volume of resection, resection index (resection volume divided by tumor volume), and rate of margin revision. RESULTS: Twenty-nine patients had SHG lumpectomy and 34 had WL lumpectomy. The SHG and WL groups were similar in age, mammographic abnormality, tumor size and type, and lymph node status. The median (interquartile range) closest margin was 5.0 (5-8) mm in the SHG group vs 3.5 (1-7) mm in the WL group (P = .01). The median (interquartile range) resection volume was 85.0 (60-128) cm(3) in the SHG group vs 143.4 (54-229) cm(3) in the WL group (P = .048). The median (interquartile range) resection index was 77.1 (51-220) in the SHG group vs 315.9 (89-3025) in the WL group (P = .003). The margin was revised in 1 (3.4%) of the patients who underwent SHG lumpectomy vs 5 (14.7%) of the patients who underwent WL lumpectomy (P = .20). CONCLUSIONS: Sonographic hematoma-guided lumpectomy is superior to WL lumpectomy in obtaining adequate margins while minimizing the volume of resection.