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The adenocarcinoma of the lung has recently shown peculiar molecular characteristics, which relate with both carcinogenesis and response to targeted drugs. Several molecular alterations have been defined as “driver oncogenes” responsible for both the initiation and maintenance of the malignancy. So far, 50% of lung adenocarcinoma has been found harbouring driver oncogenes, in which epidermal growth factor receptor pathway plays important roles. In this review, we will report mainly the advances on significance of some latest driver mutations.