Within the heterogeneous cell population of malignant neoplasms are cells with the ability to invade and metastasize. Metastatic propensity is distinctly separate from tumorigenicity alone. The complexity of the metastatic process suggests that it is controlled at the genetic level via the activation and/or deactivation of multiple genes. It is now generally accepted that there are loci in normal cells that can suppress the tumorigenic phenotype and that can be inactivated by mutation. Recent evidence from somatic cell hybridization studies and DNA transfection experiments as well as the isolation of complementary DNA clones by subtractive hybridization and by differential screening predicts that an analogous (but distinct) set of metastasis suppressor genes may exist within tumor cells that can inhibit invasion and metastasis. The interaction of the gene products of potential stimulatory and inhibitory metastasis genes may be critical in determining the metastatic phenotype of tumor cells.