BACKGROUND: Pain, patient inconvenience, vasovagal symptoms, scheduling problems, wire malposition, and a positive margin rate of 40-75% are problems commonly associated with needle localized biopsy (NLBB). Despite these issues, NLBB is still the primary means of identifying nonpalpable lesions in the breast. We hypothesized that the hematoma-directed ultrasound-guided (HUG) procedure for intraoperative localization of nonpalpable lesions would allow for lumpectomy without the downfalls of needle localization and decrease the high positive-margin rate with NLBB. METHODS: This is a retrospective study from January 2000 to October 2009. Electronic chart review identified lumpectomy procedures performed in the clinic and operating room. These patients underwent preoperative core-biopsy diagnosis by ultrasound (US) or stereotactic means. When excision was necessary needle localization or HUG was planned. A multifrequency linear array transducer was used intraoperatively for the HUG procedures, and a block of tissue surrounding the hematoma was removed. RESULTS: Localization procedures were performed in 455 patients: 126 (28%) via needle localization and 329 (72%) via HUG. The previous core-biopsy site in 100% of patients was successfully excised using HUG: 152 of 329 (46%) were benign and 177 of 329 (54%) were malignant. Margins were positive in 42 of these 177 cases (24%). was successful in 100% of patients: 88 of 126 (70%) were benign and NLBB 38 of 126 (30%) were malignant; margins were positive in 18 of these 38 (47%). Margin positivity was significantly higher for NLBB than HUG (P = 0.045, Fisher exact). CONCLUSIONS: This 10-year experience, representing the largest to date, suggests that HUG is more accurate in localizing nonpalpable lesions than NLBB. Compared with the additional painful procedure of NLBB, HUG is more time and cost-efficient. Preoperative needle core biopsy is not only the minimally invasive diagnostic procedure of choice, but also becomes the localization procedure when excisional biopsy is necessary.