Background: The aim of the study was to determine the effectiveness of mammotome biopsy (MB) in detecting preclinical breast pathologies. Material/Methods: The material consisted of 847 women, of whom, based on mammography and ultrasound, 349 patients were referred to have stereotactic mammotome biopsy (SMB) guided by digital mammography and 498 women were subjected to hand-held mammotome biopsy (HHMB) guided by US. Results: Ultimately, MB was done in 819 women. In all cases where breast carcinoma or atypical ductal hyperplasia (ADH) were detected, the patients were operated on and postoperative histopathology was treated as the reference for post-biopsy histopathology. Patients in whom post-MB histopathology detected benign lesions were subjected to a strict long-term follow-up using imaging studies. Ultimately, thanks to MB, 94 cases of breast cancer (12%) were detected as well as 725 (88%) cases of benign lesions, which corresponds to a sensitivity of 98.9% and 100% specificity. Conclusions: MB is an alternative to surgical biopsy in differentiating preclinical breast lesions. It is associated with a minimal risk of complications and may be successfully performed in an outpatient setting.