The capability to provide histologic diagnoses of nonpalpable lesions by performance of percutaneous needle biopsy has revolutionized breast imaging in the past decade. The radiologist who performs percutaneous breast biopsies assumes an increased level of responsibility for the patient regarding patient selection, lesion selection, performance of the biopsy procedure, interpretation of results, and patient follow-up. With variable and increasingly numerous options for the biopsy of breast lesions, careful attention must be paid to the selection of patients and types of lesions for different procedures. Critical technical considerations affect whether biopsy of a lesion can be optimally performed percutaneously, and these considerations must be factored into the recommendations for patient treatment. In addition, a limited preprocedural clinical assessment of the patient will allow a safer procedure to be performed expeditiously. Most breast abnormalities classified by using the ACR Lexicon as 4 (suggestive) or 5 (highly suggestive, likely malignant) are suitable for either percutaneous breast needle biopsy or needle localization and excisional biopsy. In general, those lesions classified as 3 (probably benign) carry a recommendation for early follow-up and not biopsy, because the likelihood of malignancy is small. A particular advantage of percutaneous biopsy is in the diagnosis of multicentric breast cancer. Core biopsy is less invasive and less costly than surgical biopsy, and it can be used to demonstrate multicentric disease, saving the patient a two-step surgery. However, several lesions are better treated by excision than by percutaneous biopsy. Among these are architectural distortion or loosely arranged, segmental or regional microcalcifications. For nonpalpable breast lesions visualized on mammography, sonography, or both, imaging-guided localization is required for precise needle placement either for wire localization or for percutaneous breast biopsy. The selection of which modality to use for guidance depends on (1) the adequacy of visualization of the lesion by the modality used, (2) the position of the lesion, (3) the ease of positioning the patient, (4) the skill of the operator, (5) the need to reduce radiation exposure, (6) the overall patient condition, and (7) size of the lesion. Fine-needle aspiration biopsy (FNAB) has a high sensitivity and specificity in the diagnosis of palpable breast lesions when the procedure is properly performed and interpreted. Variable results have been achieved with FNAB of nonpalpable breast lesions under imaging guidance. Three critical components are necessary to achieve reliable results by using FNAB. These include the following: (1) accuracy in needle placement, (2) skill in performance of FNAB, and (3) expert cytopathologic analysis. Accurate preoperative needle localization of nonpalpable breast lesions allows the radiologist to guide the surgeon performing an open biopsy and helps to ensure that the surgical procedure can be performed quickly and can be accomplished with the best possible cosmetic result for the patient. Lesions selected for needle localization and biopsy should undergo a complete tailored imaging evaluation before the needle localization is scheduled. Specimen radiography should be performed for all nonpalpable lesions. Once the lesion has been identified on specimen radiography, the radiologist can assist the pathologist in identifying the lesion microscopically by marking the lesion within the surgical specimen. We cover the technical and interpretative aspects of percutaneous breast biopsy and needle localization for surgical biopsy.