It is now well accepted that cancer is attributed to the accumulation of genetic alterations in the cells. Thus, to understand the molecular mechanisms of cancer metastasis, it is indispensable to identify the genes whose alterations accumulate during cancer progression as well as the genes whose expression is responsible for invasion and metastasis. Two different molecular approaches have been taken to identify such genes. One is the identification of genes whose alterations accumulate during cancer progression. The other is the identification of genes whose expression is responsible for the acquisition of metastatic potential in cancer cells. Molecular analyses of cancer cells in various stages of progression have revealed that alterations of tumor suppressor genes and oncogenes accumulate during cancer progression and correlate with the clinical aggressiveness of cancer cells. Comparative analyses of gene expression profiles between high-metastatic and non-metastatic cells have also revealed that various genes are differentially expressed in association with the metastatic potential of cancer cells. In the near future, the information obtained from these studies can be applied to the diagnosis, treatment and prevention of metastases.