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The aim of this report is to describe results of <i>BRCA1</i> and <i>BRCA2</i> Next Generation Sequencing Analysis (NGS) analysis in 132 selected Italian patients with breast/ovarian cancer. A NGS pipeline with a reliable Copy Number Variation (CNV) prediction algorithm was applied. In addition, VarSome and Priors V2.0 Software were employed for in silico analysis of novel missense variants. A total of 37 <i>BRCA1</i> and <i>BRCA2</i> pathogenic variants were found in 34 unrelated subjects with a frequency of positive patients of 25.7% (34/132). Twenty-four deleterious variants were detected in <i>BRCA1</i> (representing the 64.9% of all identified pathogenic defects) and thirteen (35.1% of all identified pathogenic variants) in <i>BRCA2</i> gene. The percentage of patients carrying a variant of unknown significance (VUS) was 7.5% (10/132). In addition, seven novel variants (five in <i>BRCA2</i> and two in <i>BRCA1</i> gene), never previously reported, were identified. Our approach represents a robust and easy-to-use method for full <i>BRCA1/2</i> screening. However, a consistent number of our high-risk families still remained without a satisfying answer. Necessarily, further collective efforts must be directed to a definitive classification of VUSs. The future auspice is that the use of multi-gene panel and more advanced screenings, such as whole exome sequencing and/or RNA seq, in routine diagnostics increases the detection rate.