Lung cancer is the leading cause of cancer death in men and women worldwide. Since the occurrence of metastases in distant organs is the major reason for mortality of cancer patients, we need to elucidate the underlying mechanisms. Many studies featuring analysis of gene expression, comparative genomic hybridization and loss of heterozygosity analysis have been performed and generated support for the hypothesis that metastatic potential is acquired early in tumorigenesis. Furthermore, it is now clear that the majority of tumor cells have the potential to metastasize. Although many changes in gene expression profiles have been established retrospectively, translational research is now a high priority to enable clinical application and treatment based on laboratory findings.