Subsets of non-small cell lung cancer (NSCLC) patients who carry activating somatic mutations of the epidermal growth factor receptor (EGFR) have demonstrated an increased probability of obtaining objective responses to the receptor tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib. However, a substantial proportion of the cases with somatic mutations, which suggest sensitivity to gefitinib, are primary resistant to it. A primary resistant case of lung adenocarcinoma that was found to carry both delE746-A750 and a G796A mutation in the EGFR is reported. In vitro, a stable clone of cells beating the G796A mutation was approximately 50,000-fold less sensitive to gefitinib in comparison to cells carrying the delE746-A750 mutant EGFR. This study suggests that screening tumour samples for a range of EGFR mutations may improve our ability to identify the patients most likely to benefit from EFGR TKIs.