Patients with advanced vulvovaginal mucosal melanoma generally have a dismal prognosis, and no effective systemic therapy for the disease has been reported. The objective of this retrospective clinical study was to assess the clinical benefit of biochemotherapy in this patient population. We evaluated the medical records of all patients with advanced vulvovaginal mucosal melanoma treated with biochemotherapy at our institution. Our search yielded 11 patients with adequate documentation for study inclusion: eight patients had undergone treatment with cisplatin (CDDP), vinblastine (VB), dacarbazine (DTIC), interferon-alpha (IFN) and interleukin-2 (IL-2), one with CDDP, VB, DTIC and IFN, one with CDDP, temozolomide and IFN, and one with CDDP, VB, DTIC, tamoxifen, IFN and IL-2. All IL-2 treatments were administered intravenously. The median follow-up duration was 10 months (range, 2-44 months). Four patients (36%) showed partial responses, but none showed a complete response. Two patients did not return for follow-up evaluation after the completion of treatment. The median time to disease progression in all 11 patients was 3 months; however, the median time to disease progression in those with a partial response or stable disease was 6 months. One patient was alive at the last documented follow-up visit (51 months). The median overall survival duration from the start of biochemotherapy was 10 months. Biochemotherapy appears to have significant activity against advanced vulvovaginal melanoma, and should be considered as a systemic treatment option for advanced, metastatic, vulvovaginal melanoma.