Malignant transformation of extragonadal endometriosis is a described. A 40-year-old multiparous woman presented with dyspareunia and dysmenorrhea. Physical examination revealed a 3 x 3.5 cm vaginal nodule. The histological examination of a bioptic sample revealed a moderately differentiated endometrioid adenocarcinoma. The patient was treated with neoadjuvant chemotherapy followed by surgery and is free from disease after 24 months. The frequency of malignant transformation of vaginal endometriosis is unknown. Obesity, hyperestrogenism, and exposure to unopposed estrogen are known risk factors, but were not present in the medical history of the present patient. In our case, preoperative chemotherapy allowed a complete resection without a vaginal demolitive surgery. This therapeutic option may be considered in order to reduce surgical resection and to preserve sexual function. However, because of the rarity of this disease, it is difficult to establish a standard treatment.