Both the contiguous and systemic theories of cancer pathogenesis are too restricting and do not consider what is now known about tumor progression during clinical evolution. A third paradigm, one that synthesizes the contiguous-systemic dialectic, has been suggested by one of us' to explain the natural history of breast cancer. This thesis argues that cancer comprises a biologic spectrum extending from a disease that remains localized to one that is systemic when first detectable but with many intermediate states. Metastases are a function of both tumor size and tumor progression. While much tumor evolution occurs during the preclinical period, we suggest that there is a progression of malignancy during the clinical evolution of a cancer. There is some evidence to support this progression of clinical cancer because pathologic grade usually correlates with tumor size, with smaller tumors being of lower grade than large ones. 7'-0 Although this may be owing in part to the more rapid growth of high-grade tumors, it is also consistent with tumor progression during the clinical evolution of the tumor. Such possible tumor progression with increasing metastatic capacity during the clinically apparent period is receiving increasing support as we learn more about the multistep nature of the development of malignancy. 1113 Once tumors become invasive, they may gradually acquire the properties necessary for efficient and widespread metastatic spread. 1 4 Therefore the likelihood, number, and even sites of metastases may reflect the state of tumor development. This suggests that there are tumor states intermediate between purely localized lesions and those widely metastatic. Such clinical circumstances are not accounted for by either the contiguous or the systemic hypotheses. The systemic hypothesis is binary: metastases either do or do not exist. If present, even if microscopic, they are extensive and widespread. The contiguous hypothesis considers systemic metastases to occur only after nodal disease; but when they occur, they are also blood borne, extensive, and widespread. From considerations of these theories of cancer dissemination, in the light of the emerging information on the multistep nature of cancer progression, we propose the existence of a clinical significant state of oligometastases. For certain tumors, the anatomy and physiology may limit or concentrate these metastases to a single or a limited number of organs. The likelihood of the oligometastatic state should correlate with the biology of tumor progression, rough clinical surrogates of which, for many tumors, might be primary tumor size and grade. Metastasizing cells may seed specific organs as a function of the seeding tumor cell number and characteristics as well as the receptivity of the host organ. The importance of" seed and soil" have been considered elsewhere 4", 5 and will not be discussed further. Tumors early in the chain of progression may have metastases limited in number and location because the facility for metastatic growth has not been fully developed and the site for such growth is restricted (this is in contrast to micrometastases, which, although small in size, are extensive in number). With further progression, the tumor seeding efficiency increases and becomes less fastidious with regard to the location of metastatic growth. In addition to this progression of malignancy, the increasing primary tumor size and therefore cell number should also be correlated with the increasing number of cells seeding. Tumor size is the principal basis of tumor staging and, with histologic grade, correlates with the likelihood of metastases. 6-106 This, we suggest, is due to the number of tumor cells …