Abstract Background: Approximately 5-10% of epithelial ovarian and breast cancer cases are hereditary and germline mutations in BRCA1 and BRCA2 genes are the most common in these patients. Prevalence of clinically relevant mutations in BRCA1/2 differs among different populations, and specifically in Brazil, a country with great ethnic diversity and miscegenation, and only limited data are available to the present moment. In our country, the public health system (SUS) is responsible for the health care of almost 75% of the population; however, genetic tests are not yet covered. Our aim was to evaluate the complete coding sequence of BRCA1/2 genes and large rearrangements in patients diagnosed with epithelial ovarian and breast cancer in the largest cancer hospital from the Brazilian public health system. Methodology: The complete coding sequence of BRCA1/2 genes were evaluated through next-generation or capillary sequencing, and large deletions were investigated through multiplex ligation-dependent probe amplification (MLPA) in four cohorts of patients: 102 unrelated patients diagnosed with epithelial ovarian cancer unselected for family history of breast and/or ovarian cancer; 89 unrelated early-onset breast cancer patients (<35 years); 42 unrelated postmenopausal breast cancer patients (> 55 years) reporting positive breast and ovarian family history; and 49 unrelated breast cancer patients selected through Frank, BRCApro, and Evans algorithms (risk > 10%). Results: Pathogenic mutation in BRCA1/2 genes was detected in 44 patients (44/282: 15.6%; BRCA1, n=27; BRCA2, n=17) featuring 33 different mutations (16 in BRCA1 and 17 in BRCA2), including two large deletions in BRCA1 (exon 1-2 deleted and exon 5-7 deleted). Five mutations were detected more than once in BRCA1 gene (c.211A>G, c.3331_3334delCAAG, c.4484G>T, c.5074+2T>C, and c.5266dupC); however, all mutations in BRCA2 gene were detected only once. Only three ovarian cancer patients had a mutation localized in an ovarian cancer cluster region (OCCR) of BRCA1 and two breast cancer patients in BRCA1 breast cancer cluster regions (BCCR). Ovarian cancer patents most commonly presented BRCA1 mutations and young breast cancer mainly presented BRCA2 mutation. In this series of patients, 24 missense variants of uncertain significance were detected (BRCA1: n=6 and BRCA2: n=18). Considering distribution of pathogenic mutation among the patient groups, a high frequency was observed in two groups: patients diagnosed with epithelial ovarian cancer (18.36%) and breast cancer patients selected by Frank, BRCApro, and Evans algorithms (18.6%). Conclusion: The chance of carrying a BRCA1/2 germline mutation in Brazilian high-risk ovarian and breast cancer patients is 15.6%. The entire gene should be analyzed as mutations are detected in various regions. Financial support: FAPESP, CNPq. Citation Format: Simone Maistro, Giselly Encinas, Tauana Nagy, Natalia Teixeira, Maria Lucia H. Katayama, Ana Carolina R. C. Gouvêa, Maria del Pilar E. Diz, Roger Chammas, Geertruida H. de Boch, Maria Aparecida A. K. Folgueira. Germline BRCA1 and BRCA2 mutations in Brazilian ovarian and breast cancer patients [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A23.