The process of metastasis is highly selective and favors the survival and growth of a few subpopulations of cells that preexist within a heterogeneous primary neoplasm. To produce metastases, tumor cells must succeed in invasion, embolization, survival in the circulation, arrest in a distant capillary bed, and extravasation into and multiplication in organ parenchyma. The outcome of this process depends on the interaction of metastatic cells with multiple host factors. To assess metastatic potential accurately, it is necessary to orthotopically implant human tumor cells recovered from surgical specimens into nude mice. This orthotopic implantation of tumor cells is invariably associated with trauma to the specific organ of implantation, which is followed by the processes of inflammation and repair. Tissue-specific growth factors may be responsible for stimulation of tumor cells that possess specific surface receptors. Understanding the factors that regulate cancer metastasis should allow for the design of rational therapy.