Large-core needle biopsy (LCNB) is a common diagnostic tool used for breast lesions biopsy under free-hand or ultrasound guidance. In this paper, we have retrospectively studied on 1,431 patients who require histopathological diagnosis of breast lesions by LCNB in Tianjin Cancer Hospital from January 2008 to April 2009. The procedure used automated prone unit, biopsy gun, and 14-gauge or 16-gauge needle under free-hand or ultrasound guidance. The pathological diagnosis and classification (12 features) were independently evaluated by pathologists. The pathological findings showed that 989 (69.1%) was invasive carcinoma, 58 (4.1%) were ductal carcinoma in situ (DCIS), 20 (1.4%) were diagnosed as atypical ductal hyperplasia (ADH), and 124 cases were benign masses. The diagnostic accuracy, sensitivity, and specificity were 0.89, 0.88, and 0.98, respectively. This study suggested that LCNB is a useful histological technique for diagnosing invasive cancer, but may not be inaccurate in diagnosis of ADH and DCIS. For the latter, surgical excision may be necessary.