The most prevalent kind of cancer worldwide and the leading cause of cancer death is lung cancer. Lung cancer is discovered at an advanced stage in 70–80% of patients. Currently used diagnostic tools do not make it possible to diagnose the disease at an early stage. The preferred methods in the treatment of lung cancer are now shifting to targeted drugs supported by molecular diagnosis. Early diagnosis of lung cancer and treatment regimen may be possible by identifying distinctive genetic markers. With advancing technology, next-generation sequencing and liquid biopsy can increase the success rates of molecular testing in clinical settings by simultaneously detecting many targets and multiple types of changes, even with small amounts of sample. This approach allows us to eliminate the disadvantages that we have experienced before, such as investigation of a limited number of targets, insufficient tumor tissue, small amounts of nucleic acid production and tumor heterogeneity, which were the reasons for failure. This chapter’s purpose is to provide a summary of the most recent techniques used to analyze genetic and epigenetic changes in lung cancer.