The switch of carcinoma cells from an epithelial to a mesenchymal-like phenotype, via a process designated 'epithelial-to-mesenchymal transition (EMT),' has been recognized as a relevant step in the metastasis of solid tumors. Additionally, this phenotypic switch of carcinoma cells has been associated with the acquisition of tumor resistance mechanisms that reduce the antitumor effects of radiation, chemotherapy and some small-molecule-targeted therapies. As multiple signaling pathways and transcriptional regulators that play a role in this phenotypic switch are being identified, novel strategies can be designed to specifically target tumor cells with this metastatic and resistant phenotype. In particular, this review focuses on the potential use of cancer vaccine strategies to target tumor cells that exhibit a mesenchymal-like phenotype, with an emphasis on the characterization of a novel tumor antigen, Brachyury, which we have identified as a critical regulator of EMT in human cancer cells.