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• Large Genomic Rearrangements (LGRs) represent a relevant proportion of BRCA variants. • The detection of BRCA mutations is relevant to PARPi therapy administration. • The demand of BRCA test performed on tumor tissue is steadily increasing. • In somatic test the evaluation of LGRs represents a great challenge. • We showed how the ddPCR is a useful method for assessing somatic BRCA LGRs. With the introduction of Olaparib as target therapy for High Grade Serous Ovarian Cancer (HGSOC) patients with germline and somatic BRCA1/2 mutations, the genetic test performed on tumor tissue has become important like the germline test. In somatic testing the evaluation of Large Genomic Rearrangements (LGRs) represents the main challenge. We describe a droplet digital PCR (ddPCR) assay for the evaluation of target BRCA1 LGRs on blood and formalin-fixed paraffin-embedded (FFPE)/Fresh Frozen Tissue (FFT) samples. We analyzed blood, FFPE and FFT samples in a validation setting of n = 78 HGSOC patients. We applied the ddPCR to BRCA1 exons 2, 20 and 21 as some of the most common BRCA1 exons involved in LGRs in our cohort of patients. The ddPCR custom assays allowed the identification of LGRs in all sample types, including FFPE specimens. Moreover, we were able to clearly detect LGRs accounted as somatic event. The introduction of ddPCR in a comprehensive workflow, encompassing both germline and somatic tests, represents an improvement in BRCA1/2 testing. ddPCR can overcome challenges related to BRCA testing, especially on FFPE analysis. Finally, ddPCR represents a promising alternative strategy to the established standard methods currently used in clinical setting. [ABSTRACT FROM AUTHOR]