Epidermal growth factor receptor signaling pathway plays an important role in pulmonary adenocarcinoma biology. Targeted therapy with tyrosine kinase inhibitors like gefitinib and erlotinib are being used in selected patients with variable response rates. Several RCT and other studies have evaluated the value of various tests such as immunohistochemistry, polymerase chain reaction, and fluorescent in situ hybridization for epidermal growth factor receptor detection. The clinical validity and applicability of these tests remain controversial. Evidence-based pathology promotes the use of systematic review of the literature and meta-analysis rather than subjective appraisal of the literature. We performed a systematic review of the literature to identify the "best evidence" regarding the use of these tests. The data were analyzed using Comprehensive meta-analysis software (Biostat, Inc, Englewood, NJ). Most of the information regarding epidermal growth factor receptor tests has been published in retrospective case series with few double-blind and prospective RCT. Estimated positive predictive values of immunohistochemistry, polymerase chain reaction, and fluorescent in situ hybridization range from 6.5% to 82%%, 7% to 100%, and 11% to 89%, respectively. Meta-analysis of nearly 5000 cases in the literature estimates that all 3 tests significantly predict response to gefitinib in patients with lung cancer. It shows lack of heterogeneity within the study results, although the current best evidence is limited by variations in study methodologies, patient ethnicity, test interpretation criteria, and variable definitions of treatment response. There is only one study evaluating the value of epidermal growth factor receptor tests in predicting response to erlotinib. Further studies are needed to clarify the predictive value of epidermal growth factor receptor tests in patients with pulmonary adenocarcinoma.