Despite great histological and molecular heterogeneity, the clinical management of highgrade ovarian carcinomas remains unspecialized. As a major subgroup, high-grade serous ovarian carcinomas (HGSOCs) require novel therapies. In addition to utilizing conventional histological prognostic markers and performing oncogenetic investigations, the molecular diagnostic method of next generation sequencing (NGS) was performed to identify ‘druggable’ targets that could provide access to innovative therapy. The present study was performed in 45 HGSOC patients (mean age, 59.1 years; range, 2587 years) with histologically proven HGSOC. Breast cancer 1/2 (BRCA1/2) germline mutations were screened in 17 patients with a familial or personal history of cancer, which was justified by oncogenetic investigations. Tumor protein 53 (P53) and phosphatase and tensin homolog (PTEN) expression were assessed in formalinfixed paraffinembedded tissues using immunohistochemistry. Somatic mutations of Kirsten rat sarcoma viral oncogene homolog, neuroblastoma RAS viral oncogene homolog (NRAS), BRaf protooncogene, serine/threonine kinase, phosphatidylinositol4,5bisphosphate 3kinase catalytic subunit α (PIK3CA) and MET protooncogene, receptor tyrosine kinase (MET) were screened using NGS on DNA extracts from frozen tumor specimens obtained at diagnosis. With a median followup of 38 months (range, 6-93 months), 20 patients are alive, 10 patients are diseasefree and 14 patients progressed within 6 months following platinumbased therapy. P53 overexpression was detected in 67% of patients and PTEN loss was detected in 38% of the patients. The overexpression of mutant P53 was found to be associated with a longer progressionfree and overall survival. In total, 2 NRAS (exon 3), 3 PIK3CA (exon 5 and 10) and 5 MET mutations (exons 14 and 18) were detected. In HGSOCs, in addition to P53 and PTEN alterations, somatic genetic abnormalities can be detected using NGS and provide molecular rationale for targeted therapies, potentially offering novel therapeutic opportunities to patients.