A case of primary malignant melanoma of the vagina is discussed. The lesion consisted of a nodule in the middle third of the vagina that was histologically suspected of being an unpigmented malignant melanoma. The melanocytic origin of the lesion was confirmed by the pattern of reactivity to a battery of human melanoma associated antigens and to class 1 and 2 histocompatibility antigens. No secondary lesions or alternative primary sites were found. The patient underwent radical hysterectomy with bilateral salpingooophorectomy, total vaginectomy and vulvectomy, radical inguinal, pelvic and paraaortic lymphadenectomy. The pathology report showed the presence of multiple neoplastic foci in the vagina. Although the removed lymph nodes were histologically free of metastases, microscopic foci of neoplastic cells were detected by immunohistochemistry in three lymph nodes. There is no evidence of recurrence at the twelfth postoperative month. Our results show that immunohistochemical techniques may usefully complement diagnostic histopathology in the diagnosis of female genital tract melanoma.