Endometrial cancer is the most commonly diagnosed gynecological malignancy. Feasibility and safety of laparoscopy are no longer to be demonstrated in patients with uterine-confined endometrial carcinoma. Vaginally assisted natural orifices endoscopic transluminal endoscopic surgery (vNOTES) is a new endoscopic approach over the past decade with significant evidence in benign pathology. Publications exploring VNOTES surgery in gynecological cancer were published first in 2014. We hereby report our first experience with vNOTES surgery in endometrial cancer. A 64-year-old patient presented with postmenopausal bleeding. Endometrial biopsy identified a G1 endometrioid adenocarcinoma. MRI suspected deep invasion of myometrium with no abnormal lymph node. She underwent a total hysterectomy with bilateral adnexectomy and retroperitoneal pelvic sentinel node biopsy by vNOTES. The final histopathology confirmed G1 endometrial adenocarcinoma FIGO II (proximal focal invasion of cervical stroma and superficial invasion of myometrium). The patient was discharged 2 days postoperatively with no complications. vNOTES offers a closer approach and a better view of afferent lymphatics and probably the best chances to identify the true sentinel node. This approach presents several advantages compared to abdominal laparoscopy such as faster postoperative recovery, reduced pain, decreased postoperative wound infections, and no abdominal trocar port complications. The future research should focus on oncological safety, accuracy, and reliability of this technique, and an international registry should help to gather rapidly these informations.