Transanal endoscopic microsurgery has been used by surgeons since 1983. All these years of experience and research have shown that this is a safe and successful approach for rectal neoplasms, both benign and malignant. The advantage of this procedure is the excellent view and hence precise surgical margins in an operative field that is otherwise difficult to reach. Furthermore, selected patients who used to require major rectal surgery now may be treated using this minimally invasive technique. These advantages may also be favorable for the gynecological field, especially in intravaginal surgery. Our case report describes the first successfully performed transvaginal endoscopic microsurgery in a woman with residual disease after treatment with chemoradiation for squamous cell carcinoma of the vagina. Despite the difficulty of operating in tissue with post-radiation effect, the rest of the tumor was excised with clear surgical margins without damage to the rectum. The patient was discharged from the hospital 2 days after the procedure and recovered without complications.