The identification of somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in non-small-cell lung cancer (NSCLC) and their correlation with response to EGFR inhibitors has become an important event in the fields of cancer genetics and therapeutics. The initial observation of a higher response to gefitinib and erlotinib in patients of Asian origin was followed by the discovery that they harbor more frequent EGFR mutations in NSCLC; this raises the issue of ethnic diversity in the pathogenesis of given tumors. In a similar fashion, amplification of the closely related HER2 gene, which could also have implications for the treatment of NSCLC, is also more frequent in East Asian patients. On the other hand, EGFR gene amplification may be more prevalent in Western populations. The implication of these findings is that ethnicity may indicate different genetic backgrounds in common tumors that may influence clinical outcome and response to therapy. Therefore, in clinical trials with tyrosine kinase inhibitors and other molecular-targeted therapies, the inclusion of a global population appears to be required. © 2006 by American Society of Clinical Oncology.