Gefitinib is an EGFR TKI with a response rate of 10% in unselected patients with advanced NSCLC in the U.S. However, patients with NSCLC who are never smokers or have features of bronchioloalveolar lung cancer have response rates of 25-50%. At present, this "targeted" therapy is given to patients with advanced NSCLC regardless of whether EGFR signaling is a critical driver of their tumor's growth. Recent data would suggest that mutations in the EGFR tyrosine kinase domain correlate with response in small retrospective studies conducted in patients with advanced NSCLC. This is a prospective study in patients with Stage I and II NSCLC who have features that correlate with response (never or minimal smokers and features of BAG) to "enrich" for response to gefitinib. Fifty patients who are candidates for surgery will be treated on this study; we will obtain fresh frozen tissue by core biopsy before treatment with gefitinib after which patients will be treated with at least 21 days of gefitinib pre-operatively. Patients will be assessed for response by repeat CT scan after gefitinib therapy and subsequently undergo surgical resection; additional fresh frozen tissue will be procured at surgery. Patients with a response to gefitinib therapy and/or patients with EGFR mutations identified from core biopsy will continue "maintenance" gefitinib for 2 years after surgery. The primary endpoints of this study are (1) Correlate the presence of mutations in the tyrosine kinase domain of EGFR gene and radiographic response prospectively in patients with Stage I/II NSCLC patients; (2) Determine kinase activity of specific mutations as assessed by phosphotyrosine activity and autophosphorylation of EGFR in transient transfection assays and sensitivity to gefitinib as compared to wild-type EGFR. Secondary Endpoints are (1) Identify gene(s) or gene clusters that exhibit changes in gene expression before and after treatment with gefitinib, and identify significant differences in gene expression between sensitive and resistant tumor, using microarray analysis; (2) Determine time to recurrence and survival in patients with Stage l/ll NSCLC patients treated with "maintenance" gefitinib. Further characterization of tumors harboring these mutations, may have significant therapeutic implications for patients with NSCLC and change the paradigm whereby we treat patients with NSCLC.