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An inductive argument of metastasis with a metaphor of seed and soil was made by Stephen Paget in 1889. It is commonly held that metastasis is dependent on both the organ from which the primary tumors originate, and the organs to which the tumor cells travel. The assumption is based on the statistical observation of a number of autopsy samples. Here I attempt to establish a theory on the mechanisms of metastasis with experimental evidence. I propose that dysregulation of pro-inflammatory Toll-like receptor 4 signaling, stimulated by its endogenous ligands, establishes pre-metastatic soil. Once specific parameters are established, deductive judgments could be possible to predict to which organ a given tumor metastasizes. (Cancer Sci 2009)