Ultrasound-guided, large-core needle biopsy (US-LCNB) of suspicious breast lesions is acknowledged as less invasive and less expensive and less time consuming than surgical biopsy, and provides a histologic diagnosis with a comparable high degree. US-LCNB has been proven to help reduce the number of unnecessary surgeries for benign disease. Its limitations, however, are false-negative results and underestimation of disease. Thus, the demand for breast teams is to carefully adhere to the principles of triple assessment and imaging-histologic correlation, and follow-up of lesions with a specific benign histology after biopsy. Also, the acceptance of guidelines and rigorous quality controls help to reliably minimize the delay in the diagnosis of breast cancer in patients with false-negative biopsies. This paper aims to summarize the equipment and methods as well as the benefits and limitations of US-LCNB. Also, guidelines of quality assessment are suggested. Finally, recent developments which may help to overcome the limitations of US-LCNB will be discussed, i.e., directional vacuum-assisted biopsy (VAB), three-dimensional (3D) US-guided biopsy, as well as the use of tissue harmonic imaging (THI) and compound imaging (CI) during biopsy.