Herein we discuss the factors that bring about the transformation of epithelial cells into cells of fibroblastic phenotype. This type of transformation, referred to as epithelium-to-mesenchyme transition (EMT), allows cells to dissociate from the epithelial tissue from which they originate and to migrate freely. EMT is therefore thought to play a fundamental role during the early steps of invasion and metastasis of carcinoma cells. Among biological agents which have been identified as inducers of EMT are a number of cytokines and extracellular matrix macromolecules. The coordinated changes in cell morphology, associated with the induction of cell motility and the disruption of intercellular junctions, are the consequence of a signaling cascade emanating from the plasma membrane and leading to changes in gene expression. Understanding the mechanisms regulating EMT of normal and transformed epithelial cells may offer new perspectives for designing therapies for the treatment of metastatic cancers of epithelial origin.