Sixteen patients with invasive thymoma (stage III and stage IVA) were treated with chemotherapy and then operation. All tumors were considered nonresectable after first staging, and patients were treated with the following chemotherapy in 4-day courses, administered intravenously: cisplatin (50 mg/m2) and doxorubicin (40 mg/m2) on day 1, vincristine (0.6 mg/m2) on day 3, and cyclophosphamide (700 mg/m2) on day 4. The courses were repeated every 3 weeks, and toxic effects were well tolerated. Seven patients (43%) had a complete remission, and nine patients (57%) had a partial remission, with an overall complete remission plus partial remission rate of 100%. After chemotherapy all patients underwent operation. We performed 12 sternotomies and four posterolateral thoracotomies. At operation 11 patients had radical resection and five had partial resection. We administered radiotherapy in 11 patients who had histologically demonstrated tumor after operation. In five patients, the specimen showed only fibrosis; these patients received three cycles of chemotherapy but not radiotherapy. Median survival was 66 months with a 3-year survival of 70%. We believe that neoadjuvant chemotherapy with surgical intervention is justified for advanced invasive thymoma; a longer follow-up and a larger number of patients will determine the impact of this treatment on long-term survival.