There is an increasing need of molecular diagnosis with clinical utility to predict post-operative tumor recurrence and to select patients most likely to have benefit from certain therapeutics in cancer therapeutics. Recent studies further disclosed the biological and immune landscapes of various cancers leading to the development of potential biomarkers carrying prognostic and/or therapeutic relevance. Emerging integration of molecular profiling datasets has led to the identification of distinct molecular subtypes with diverse clinical behaviors and potential sensitivity to various therapies even for cancers with the same histological features and same stages. It has also led to the disclosure of frequently altered genes and proteins that could lead to perturbation of intracellular signaling pathways and their microenvironment. In the present presentation, we will discuss the changes in the paradigm of molecular diagnostics in lung cancer.