Chemotherapy or chemoradiation is often used in Stage IIIA non-small cell lung carcinoma before surgical resection (neoadjuvant therapy). In reviewing the histopathology of such tumors after resection, the recognition that the pathologic changes are related to prior therapy and the assessment of tumor regression are both of importance. To refine histologic parameters for tumor regression and describe patterns of tumor reaction to therapy, we identified 30 lobectomy or pneumonectomy specimens from 1996-2000 in which neoadjuvant therapy was received before surgical resection. Histologic patterns of treatment-induced tumor regression were analyzed semiquantitatively and included necrosis, fibrosis, mixed inflammatory infiltrate, foamy macrophages, and giant cells. To identify clinical and histologic parameters that correlate with treatment response, the 30 specimens were graded for tumor regression. No correlation was found between tumor regression and age, gender, or type of therapy (chemoradiation versus chemotherapy alone). Squamous cell carcinoma showed a significantly higher rate of response than adenocarcinoma (P =.04), with a significant number of adenocarcinomas in the nonresponder subgroup (P =.05). Tumor size reduction by radiologic assessment, when compared with histologic regression, did not reveal a statistically significant association. However, a positive correlation was found between extent of fibrosis and radiologic estimate of size reduction.