Between January 1988 and June 1990, seven previously untreated patients with histologically confirmed and clinically staged IIIa invasive thymoma (IT) were enrolled in a prospective, single treatment arm study of neoadjuvant chemotherapy (NC) followed by surgery and postoperative radiation therapy (4600 to 6000 cGy). The NC included three cycles of cisplatin (75 mg/m2 on day 1), epirubicin (100 mg/m2 on day 1), and etoposide (120 mg/m2 on days 1, 3, and 5), every 3 weeks. All patients showed a partial response (greater than 50%) and underwent complete (n = 4) or incomplete (gross [n = 1] or microscopic [n = 2] residual tumor) surgical resection. Histologic examination was negative for two completely resected patients. Projected 2-year survival was 80%; all patients but one currently are alive and disease-free. This approach appeared to be feasible and may be a new therapeutic choice in the management of IT, but its use on a regular basis should be reserved until a larger number of patients and longer follow-up are available.