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During the last 20 years an ever increasing number of nonpalpable breast lesions (NPBL) have been identified. A cytohistological definition is required to establish the correct diagnostic classification of these lesions and the suitable therapy to be used. The Fine-Needle Aspiration Cytology (FNAC), the Advanced Breast Biopsy Instrumentation (ABBI) system or the Vacuum Assisted Core Biopsy (VACB) represent valid alternatives to the surgical excision with needle localisation. 591 NPBL have been included in the present study. The suspected grade of each lesion was then assigned according to the Breast Imaging Reporting and Data System (BI-RADS) of the American College of Radiology. All the BI-RADS 4 and 5, and all the BI-RADS 3 lesions, which after 6-month follow-up showed altered morphology, were sampled for cytological and/or histological examinations by FNAC, VACB or biopsy by ABBI system. The diagnostic algorithm used in this study obviated a surgical procedure in 574 women (97.1%), yielding a 73.9% decrease in the cost of diagnosis compared with surgical biopsy, and a 48.1% decrease in cost if all lesions had been histologically tested using ABBI or VACB procedure. Compared to surgical biopsy, VACB and ABBI system are less expensive, and have smaller emotional and aesthetical impact on patients; however they retain the same sensitivity and specificity.