A thorough understanding of the limitations of sampling and histopathologic issues affecting lesion management is critical to successful large-core (14-gauge) needle breast biopsy. The most common problems are differentiating usual hyperplasia, atypical hyperplasia, and carcinoma in situ; satisfactory sampling of microcalcifications, often present in adjacent benign and malignant processes; differentiating phyllodes tumor from cellular fibroadenoma; and assessing the extent of an in situ component in mixed invasive and in situ carcinoma. Equally important is understanding what constitutes an acceptable histopathologic result given the mammographic appearance of the lesion. Mammographers and pathologists need experience in identifying benign processes that can manifest as discrete masses at mammography and core biopsy: focal fibrosis, apocrine metaplasia, sclerosing adenosis, and fat necrosis. When present as discrete histopathologic processes at core biopsy, such diagnoses should be accepted. Nonspecific diagnoses such as "benign breast tissue" should be avoided by pathologists when a discrete process is evident; absence of a discrete finding to explain the mammographic appearance should prompt repeat core or excisional biopsy.