The development of a metastasis is dependent on an interplay between host factors and intrinsic characteristics of malignant tumor cells. The process of metastasis is highly selective, and the metastatic lesion represents the end point of many destructive events that only a few cells can survive. Neoplasms, which are predominantly heterogeneous, contain a variety of subpopulations of cells with differing metastatic potential. Furthermore, metastatic cell variants have been shown to preexist in murine neoplasms of old and recent origin. The possible existence of highly metastatic variant cells within a primary tumor suggests that we no longer should consider a neoplasm to be a uniform entity. Efforts to design effective therapeutic agents and procedures against malignant tumors should be directed toward the few but fatal metastatic subpopulations of cells.