We describe a new dedicated ultrasound system for computer-guided large core breast biopsy (LCBB) and report our first clinical experience in 45 female patients. After an initial 30 biopsy procedures on a US breast phantom, LCBB using this new system was performed in 45 non-palpable surgically verified breast lesions. All biopsies were performed by the same radiologist using 14-gauge long-throw biopsy needles. Histological results following LCBB were compared with open surgical biopsy. Procedure time and any complication arising was registered in all procedures. Biopsies using this prototype were successful and yielded sufficient material in all 45 lesions. There were 23 benign and 22 malignant lesions with complete histological agreement between LCBB and open surgical biopsy in 44 of the 45 lesions. In one invasive ductal cancer the pathologist could only state high probability of malignancy but not give a definite diagnosis. Besides one case with early termination due to decreased visibility of the target lesion, no technical complications were noted. Slight vasovagal reactions were seen in 4 patients but did not alter the histological results. The average procedure time was 30+/-2.7 min. This new dedicated US system for computer-guided LCBB is an accurate and safe method for diagnosing breast lesions. Although this new system may have no major impact for US-guided LCBB experienced physicians, it might be a promising alternative for the non-skilled physician to currently available breast biopsy techniques.