Trefoil factors (TFF) belong to a family of heat, acid, and protease-resistant regulatory peptides ubiquitously expressed in the brain, blood, and peripheral organs. In inflammatory conditions and generation of cancer lesions, they are induced, lost, or modified by gene silencing and somatic mutations. Thus, TFF overexpression or invalidation is either the consequence or the causal origin of human solid tumors and their progression to metastatic situations. While the TFF receptors or recognition systems are not still clearly identified, TFF are involved in mucosal and epithelial cell cytoprotection, wound healing, cancer cell survival and invasion, and angiogenesis, through several oncogenic pathways involved in neoplasia. Finally, TFF are...