The BRCA1-BRCA2 genes predispose to hereditary breast and ovarian cancer, and the germline and mutational status of these genes defines a target population that can benefit from PARP inhibitor treatments. To respond to the increasing number of BRCA1-BRCA2 tests, it is necessary to shift to high-throughput technologies that are reliable and less time consuming. Different methodological platforms are dedicated to this purpose with different approaches and algorithms for analysis. Our aim was to set up a cost-effective and low time-consuming BRCA1-BRCA2 mutation detection workflow using the Ion Torrent PGM technology. A retrospective cohort of 40 patients with familial breast/ovarian cancer previously tested by Sanger sequencing and a prospective cohort of 72 patients (validation set) were analyzed. The validation set included 64 patients affected by familial breast/ovarian cancer and eight sporadic ovarian cancer cases, who are potential candidates for PARPi treatments. A complete and standardized workflow easily usable and suitable in a certified laboratory has been proved and validated. This includes all steps from library preparation to the final report. The use of next-generation sequencing will be of benefit for patients enrolled in the genetic counseling process and, moreover, will enhance the process of selecting patients eligible for personalized treatments. © 2016 Wiley Periodicals, Inc.