To prospectively evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy locally advanced or recurrent vulvar carcinoma, 58 patients referring for primary (41) or recurrent (17) disease received preoperative external radiotherapy to a dose of 54 Gy, divided into two courses with an interval of 2 weeks. 5-Fluorouracil (750 mg/m2 daily for 5 days) and mitomycin-C (15 mg/m2 single bolus) were given at the start of each cycle. Wide local excision and inguinal lymphadenectomy were planned after treatment. Eighty-nine percent of patients completed the chemoradiotherapeutic treatment, whereas 72% underwent surgery. Objective responses were observed in 80% of vulvar diseases and in 79% of groin metastases. Pathologic complete response of both the vulvar and inguinal disease was confirmed in 13 patients (31%). Early severe toxicity was recorded in 3 patients and severe worsening of performance status in 3. Three deaths occurred shortly after treatment and at least one is directly related to toxic effects. This treatment allows good control of locally advanced and recurrent vulvar cancer with acceptable side effects. Further follow-up is required to determine the long-term outcome and the effectiveness of the surgical procedure.