The purpose of this study was to evaluate the diagnostic value of a self-contained battery-driven vacuum-assisted breast biopsy (VABB) system for the sampling of breast masses under ultrasound guidance. Sixty-five patients with 70 lesions underwent percutaneous 10-gauge ultrasound-guided VABB using the coaxial technique. In 38 lesions, subsequent surgery and comparison of histology was performed. The remaining 32 cases were followed-up and defined as true negative after a cancer-free interval of 24 months. VABB revealed malignant histology in 28 (40%) cases. Twenty-four malignancies were confirmed after surgery. Four invasive cancers verified in VABB were not found during surgery because they were completely removed, as proved by a disease-free interval of 24 months. One cancer missed in ultrasound-guided VABB due to its small size was successfully diagnosed with stereotactic VABB and thus turned out to be false negative, resulting in an overall sensitivity of 96.6%. Forty-one patients were free of cancer during the follow-up period of at least 24 months. In conclusion, the self-contained VABB device is well suited for ultrasound-guided breast biopsies.