The minimally invasive technique of stereotactic core needle breast biopsy threatens to replace surgical excisional biopsy as the preferred method to diagnose most mammographic abnormalities. The goal of this study is to evaluate the ability of stereotactic core needle breast biopsy to accurately assess suspicious nonpalpable masses and calcifications on mammography. A prospective protocol was initiated which called for stereotactic core needle breast biopsy instead of traditional excisional biopsy to assess suspicious calcifications and masses noted on mammography. A minimum of five core biopsies are excised by a radiologist, histologic evaluation is performed by the department of pathology, and clinical correlation between the radiographic and pathologic findings is assessed by the surgeon. Malignant lesions are appropriately treated and clearly benign lesions are followed mammographically. During the initial 18 months after the protocol was activated, 451 patients were evaluated by stereotactic core needle breast biopsy. There were 367 benign cases documented by stereotactic core needle breast biopsy and 84 malignant cases. One benign stereotactic core needle breast biopsy case proved to be malignant at subsequent surgical biopsy and one malignant stereotactic core needle breast biopsy case could not be confirmed at subsequent surgical biopsy. The results of this study demonstrate that stereotactic core needle breast biopsy provides accurate histologic evaluation of mammographic abnormalities. A multidisciplinary approach to include radiologist, pathologist, and surgeon is critical to ensure a thorough and accurate assessment of nonpalpable breast lesions.