Primary villoglandular adenocarcinomas of the vulva are rare, and only seven cases have been described to date. Hypotheses about the origin of this neoplasm remain highly speculative. We report the case of a 58-year-old woman who developed this very uncommon malignant tumor. Immunohistochemical studies of the tumor revealed positive staining for cytokeratins 7 and 20 and a negative staining for estrogen and progesterone receptors. Special stains showed the presence of intracellular mucin. No other primary lesion was found on clinical evaluation and extensive investigation. The patient was first treated by radical hemivulvectomy, followed by ipsilateral inguinal lymph node dissection and laparoscopic right salpingo-oophorectomy for an incidental finding of an ovarian cyst. The patient remained free of disease 16 months after the initial surgery.