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Background Vacuum-assisted breast biopsy (VABB) has been routinely recommended for stereotactic intervention in cases of isolate mammographically-detected calcifications. Herein we aimed to evaluate and compare the diagnostic consistency and accuracy of calcified and noncalcified specimens obtained from same sites of sampling on mammography-visible calcifications. In addition, we presented the biopsy procedure and retrospectively evaluated the usefulness of VABB as well as the complications of this technique over an eight-year experience in our centre. Methods This single-institution observational cohort study included 587 patients referred for stereotactic 11-gauge VABB of 594 mammographically-detected calcifications between January 2010 and December 2018. The rate of histopathological underestimation, the false negative, the diagnostic consistency and accuracy between calcified and noncalcified specimens of VABB were comprehensively evaluated based on the surveillance data and final histopathological result of the surgical specimens. Results In total, 594 biopsy procedures were performed in 587 patients (mean age 46 years, range, 21-80 years). The average number of biopsy specimens was 14.7 (range, 9-21) per lesion. VABB pathological results revealed 471 (79.3%) benign, 39 (6.6%) high-risk, and 84 (14.1%) malignant cases. The diagnostic inconsistency between calcified and noncalcified specimens was 14.6% (105/123) for high-risk and malignant lesions. Furthermore, calcified specimens exhibited higher diagnostic accuracy of malignant lesion as compared with the noncalcified specimens (97.7% versus 82.6%, respectively). Underestimation rate for high-risk lesions and in situ carcinoma was 5.1% and 54.1%, respectively, along with a false negative rate of 6.25%. In addition, mild complications were reported with high patient tolerance. Conclusions Stereotactic 11G-VABB might be preferred for the investigation of non-palpable mammographically-detected calcifications in terms of accuracy and safety profile. The high prevalence of diagnostic discordance between the specimens with and without calcifications revealed a higher value of calcified specimens in diagnosing high-risk and malignant calcifications.