Over a decade since the discovery of EGFR mutation, and 6 years since prospective clinical trial data proved that routine molecular pathology tests improve survival in stage IV lung cancer, there is still debate whether to test patients with earlier stages of disease (stage I-III). As discoveries of targeted drugs for stage IV patients accelerate-prompting routine testing for ALK, ROS1, RET, BRAF V600E, and HER2, among others-there is an argument that all lung cancers should be genotyped for the purpose of classification, regardless of stage of disease. The counterargument is that because targeted drugs have only been validated for use in stage IV disease, these molecular tests need only be conducted at the time of disease recurrence. This review will describe current, practical applications of molecular pathology testing in early stage lung cancer, focusing on the immediate diagnostic, prognostic, and therapeutic implications for individual patient management. Meanwhile, large-scale clinical trials are underway to test targeted drugs as adjuvant therapies in patients with early stage disease.