Here, we present autocrine activation of EMT through the TGF-β/Crk axis, and now hypothesize that in the initial stage of human cancer, each tumor cell has been exposed to various stimuli secreted from the fibroblasts or macrophages, and among them, TGF-β may enhance Crk levels in an individual cancer cell and lead to an EMT phenotype together with expression of both TGF-β and its receptor. The gene discussed is CRK; the disease is neoplasm.