Breast calcifications pose a significant diagnostic and procedural dilemma. We evaluated en bloc stereotactic excision of indeterminate and suggestive microcalcifications for histologic diagnosis using a large-bore cannula biopsy device. We retrospectively reviewed 61 groups of microcalcifications removed with a large-bore cannula biopsy device from 59 patients (age range, 35-72 years old). The cannula diameter was 20 mm in 47 cases, 15 mm in nine cases, and 10 mm in five cases. The median lesion diameter was 6.6 mm (range, 4-17 mm). The procedure was performed by radiologists in an outpatient setting, with patients undergoing local anesthesia. All patients with a diagnosis of malignancy underwent surgery. In all instances, microcalcifications were removed in a single pass, in a single intact tissue specimen, through a maximum skin incision of 2 cm (0.8 inch). Twenty-five malignancies, 34 benign lesions, and two cases of lobular carcinoma in situ were identified. Sixteen malignancies were noninvasive and nine were invasive. No residual tumor was found at surgery in six of the 18 cases with involved margins and in five of the seven cases with uninvolved margins. One case of lobular carcinoma in situ with involvement of the margins additionally showed ductal carcinoma in situ at surgery. Mammographically identified microcalcifications are excised en bloc with the large-bore cannula biopsy device, providing a stereotactically localized tissue sample that is comparable with that obtained with open surgical biopsy and allows evaluation of the margins. This surgical radiologic procedure may represent a valid alternative, in selected patients, to conventional surgical biopsy after radiologic localization.