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Multi-target stereotactic core-needle breast biopsy (MSBB) with large core needles is a modern and effective method to quickly determine the histologic nature of non-palpable breast lesions in an easy ambulatory setting. The number of patients with mammographically detectable, suspicious breast lesions is constantly increasing due to enhanced breast cancer awareness in Western female populations and with expanding screening mammography activities. MSBB is a minimally invasive diagnostic procedure, performed on an ambulatory basis under local anaesthesia in the prone position on a specially constructed stereotactic biopsy table. The patient is able to resume normal activities 1 h after the biopsy procedure. Technical and medical complications are extremely rare. In our study, we analysed the histological results of 426 MSBB procedures in 389 consecutive female patients during the years 1998-2002, and in 91 cases we were able to compare the histologic results of MSBB with the definitive histology of subsequent excisional biopsies. MSBB was technically successful in 415 out of 426 procedures (97.4%). The sensitivity for malignancy was 94.6% (87 out of 92). MSBB, therefore, is to be qualified as a remarkably reliable, patient-friendly and economic diagnostic breast intervention and was well tolerated and highly accepted by virtually all female patients involved in this single-institution feasibility and effectiveness study.