Over the past decade, significant progress has been made in the characterization of molecular abnormalities in non-small cell carcinoma (NSCLC) tumors, mostly adenocarcinomas, that are being used as molecular targets and predictive biomarkers for the selection of patients for targeted therapy. These recent advances in NSCLC targeted therapy require the analysis of a panel of molecular abnormalities in tumor tissue specimens, including gene mutations (e.g., EGFR, KRAS, BRAF, DDR2), gene amplifications (e.g., MET, FGFR1), gene fusions (e.g., EML4-ALK, RET-KIF5B, ROS) and protein expression (e.g., EGFR, c-Met), by applying different methodologies to tumor tissue (biopsy) and cell (cytology) samples. However, the biopsy and cytology samples available for molecular testing in advanced metastatic NSCLC tumors are likely to be small specimens, including core needle biopsies (CNB) and/or fine needle aspiration (FNA), which may limit the molecular and genomic analysis with currently available methodologies and technologies. The utilization of novel technologies, including next-generation of sequencing platforms, will allow the analysis of multiple genetic abnormalities using very small amount of tumor tissue specimens. The role of the pathologist is becoming increasingly important to adequately integrate both routine histopathology assessment and molecular testing into the clinical pathology for tumor histology diagnosis and subsequent selection of the most appropriate therapy. At the conclusion of this activity, the learner will be able to do the following: 1. Summarize the most important molecular abnormalities than can be used to direct targeted therapy in non-small cell lung carcinomas. 2. Explain the importance of adequate sampling of tumor tissue for molecular testing of lung cancer.