Nowadays, thanks to next generation sequencing, it is simultaneously possible to search for driver mutations in hundreds of cancer-related genes with high sensibility and specificity, by exploiting formalin-fixed paraffin-embedded tumor material, from biopsy samples and surgical specimens, or circulating tumor DNA in the patient's blood. In addition to indicate the genomic alterations, this modern technology provides information about: the approved therapies in the patient’s cancer type or in other tumor types for a personalized oncology; potential clinical trials; mutational burden and microsatellite instability (MSI). This last datum is particularly relevant because the U.S. Food & Drug Administration (FDA) has approved the use of pembrolizumab for all unresectable or metastatic, MSI-high or mismatch repair deficient, solid malignancies, among which there are 17-32% of sporadic endometrial carcinomas and 10-17% of sporadic ovarian cancers. Similarly, the FDA has approved olaparib for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer, characterized by deleterious or suspected deleterious germline or somatic mutations in ‘breast cancer’ (BRCA) genes, who are in complete or partial response to first-line platinum-based chemotherapy. Therefore, we are facing an era of innovation in gynaecological oncology, in which molecular profiling is joining immunomorphological typing for new health goals.