The detection of variants of uncertain significance (VUSs) in BRCA1/2 genes poses challenges in counseling and managing cancer patients. In this work, we have reviewed all BRCA1/2 VUSs detected in our clinical service in Bologna (Italy) over the past 11 years following recently developed classification guidelines, yielding a classification rate of 81.3%. This result demonstrates the effectiveness of the new guidelines and, above all, allows to give a clear and definitive result to the 197 patients carrying the classified variants, who will benefit from more accurate clinical management for themselves and for their family members. (https://jmg.bmj.com/content/early/2023/12/30/jmg-2023-109694 )