The multimodality approach to locally advanced Stage III non-small cell lung cancer is continuing to evolve. In this trial, 54 patients with surgically staged IIIA disease were treated with neoadjuvant chemotherapy, surgical resection, and chest radiotherapy. Response to four cycles of CAP chemotherapy (cyclophosphamide, doxorubicin, cisplatin) was 39% (8% complete responses). One septic death occurred. Thoracotomy was performed on 31 patients, of whom 29 (56%) were resected and 24 (44%) were completely resected. Complete resections were more frequently observed in chemotherapy responders. Extranodal mediastinal extension in nonresponding patients was the most frequent reason not to attempt thoracotomy. The overall median times to progression and survival were 11.6 (.7-66.5) and 17.9 (2.8-71.4) months. Long-term disease-free survival was observed in 11 patients (20%) with a median follow-up of 46.5 (24-71) months. All these patients underwent complete resection and constitute 46% of the patients undergoing complete resection. Median times to progression and survival were 33.4 (5.0-66.5) and 33.5 (10-71.4) months for completely resected patients. Although the ability to perform surgery identified a population that has favorable locoregional control and disease-free survival, distant relapse continues to represent the major obstacle to enhanced survival in resected patients. Unresected patients, however, are likely to relapse in both local and distant sites. Response to chemotherapy may not only enhance systemic control, but may also increase the probability of complete resection. Randomized trials should be conducted to evaluate the role of individual modalities (surgery, chemotherapy, or radiotherapy) while applying the remaining modalities maximally. The temptation to compare different treatment approaches should be resisted.