Vaginal carcinosarcomas (VCSs) are rare and clinically aggressive neoplasms. Primary vaginal malignancies are among the rarest malignant tumors, so clear management guidelines and optimal therapy, especially in the presence of significant pelvic organ prolapse, has not been determined. Here, we present a case of primary VCS closely associated with differentiated squamous intraepithelial neoplasia (DSIN), from which it appeared to have arisen in a postmenopausal patient with complete uterine prolapse. The unusual presentation of our case with DSIN in the adjacent vaginal epithelium with possible diagnostic pitfalls emphasizes the need for systemic presentation of these cases to help pathologists and clinicians know that such lesions can initially present in a patient with complete uterine prolapse. To our knowledge, this is the first case of vaginal DSIN described in the literature to date.