The aim of this study was to evaluate the safety and feasibility of a single-port system for transoral endoscopic thyroidectomy with vestibular access (TOETVA). Two embalmed human cadavers were used to test the single-port technique. After positioning, a median vestibular incision was made. Adipose tissue was dissected through the mentum with a Kelly clamp to reach the subplatysmal level. The Keyport Single Port System (Richard Wolf) was then inserted. After port placement, flexible endoscopic dissectors and a 5-mm endoscope were advanced. After removing the dissectors, we inserted the ArtiSential laparoscopic instruments. We also used a 3-port TOETVA on another human cadaver to compare the results with those of the single-port surgery. In the first cadaver, skin tension was observed during trocar insertion and dissection. Trocar insertion resulted in skin perforation in the submental area. In the second cadaver, the single-port trocar was successfully inserted despite the significant skin tension. However, the trocar did not allow the necessary surgical maneuvers to proceed with subsequent surgical steps and create a working space. Postprocedural anatomic dissection revealed that the distal branches of the mental nerve were related to the trocar passage. Our cadaver study demonstrated that single-port TOETVA is unsafe and not feasible with the current technology of the Keyport single-port system. This approach needs to be improved to perform this technique without injury to distal branches of the mental nerve, skin perforation, and other complications.