The development of breast cancer screening has radically changed the diagnostic approach to breast lesions. Stereotactic large-core breast biopsy was developed to reduce the number of unnecessary surgical excisional biopsies in the increasing number of patients with doubtful or suspicious mammogram findings. The methods used to evaluate this new technique are discussed, as well as results in terms of efficacy, factors that may influence efficacy, and difficulties in interpreting large-core biopsies. Recommendations regarding the harvesting and interpretation of stereotactic large-core biopsies are made.