The last two decades have seen an exponential growth of our knowledge on the molecular biology of cellular processes and neoplastic transformation. There is high expectation that these advances will be translated into further improvement in the care of cancer patients, especially in the areas of prevention, diagnosis and treatment. Realizing that the histopathological classification of lung cancer has reached its limit in providing additional critical information to further improve treatment strategy, numerous molecular aberrations occurring in lung cancers have been explored as potential new diagnostic markers and markers for molecular sub-staging. Despite extensive studies, most results remain largely controversial. This manuscript will briefly review molecular/genetic changes that have been investigated as candidate diagnostic, prognostic and predictive markers and as biomarkers for early detection in lung cancer. A more concerted and global approach to study the clinical relevance of molecular changes in lung cancers is required in the future.