Since its description in Sweden in the 1970s,1 stereotactic biopsy has been increasingly used for breast diagnosis. Stereotactic biopsy provides an accurate, safe, and cost-effective alternative to surgical biopsy for mammographically evident lesions.2 Although early studies of stereotactic biopsy used fine needles, fine needle aspiration has many limitations including benign nonspecific diagnoses, incomplete characterization of both benign and malignant lesions, and insufficient samples.3 The limitations of the fine needles led to the development of techniques for stereotactic biopsy using larger tissue acquisition devices including automated core needles and directional vacuum-assisted biopsy probes. This chapter discusses the accuracy, safety, cost, indications and contraindications, equipment, and technique of stereotactic core biopsy and gives specific suggestions for biopsy of challenging cases.