Evaluation of: Hirsch FR, Varella-Garcia M, Bunn PA Jr et al.: Molecular predictors of outcome with gefitinib in a Phase III placebo-controlled study in advanced non-small-cell lung cancer. J. Clin. Oncol. 24(31), 5034-5042 (2006) [1] . In this article, we critically evaluate a recent publication that assessed molecular predictors of clinical benefit from treatment with gefitinib, a small-molecule inhibitor of the epidermal growth factor receptor (EGFR), in patients with advanced non-small-cell lung cancer. EGFR inhibitors, such as gefitinib, have previously been shown to preferentially benefit distinct subgroups of advanced non-small-cell lung cancer patients, and strategies to prospectively identify these subgroups are under active investigation. In this study, the authors analyzed tissue from a randomized Phase III trial to examine the association of clinical benefit after gefitinib treatment with EGFR protein expression, EGFR gene copy number, EGFR mutations and other potential predictive markers. The paper by Hirsch and colleagues will be discussed and compared with other studies of potentially useful EGFR biomarkers.