Primary vaginal adenocarcinoma unassociated with antenatal diethylstilbestrol (DES) exposure is extremely rare. The strategy for treating this disease has not yet been established due to its rarity and, therefore, the prognosis remains poor. A 69-year-old woman presented with vaginal bleeding but no history of antenatal DES exposure. She had a solid tumor in the recto-vaginal space, diagnosed as FIGO stage III vaginal adenocarcinoma. After neoadjuvant chemotherapy consisting of paclitaxel and carboplatin, the tumor became undetectable. Thereafter, radiotherapy was applied to the pelvis and vagina in order to reinforce the state of remission. The patient remains free from recurrence 1 year after discharge. The present case was successfully treated with chemotherapy and radiotherapy, suggesting that chemotherapy may be an option for the treatment of this type of tumor.