Tumor metastasis-the spreading of primary tumor cells to distal organs - is the major cause of death of cancer patients. The metastatic process consists of four distinct steps, invasion, intravasation, extravasation, and metastatic growth, and primary tumor cells need to acquire different genetic characteristics to accomplish each step. The main players during the metastatic process remain, however, largely unknown. A recent report in Cell by Robert Weinberg's group (Yang et al., Cell 2004;117:927-39) adds the transcription factor Twist to the list of metastatis regulators. Suppression of Twist expression in tumor cells inhibits the metastatic potential, whereas its overexpression induces an epithelial-mesenchymal transition (EMT) in epithelial cells. This study provides direct evidence that EMT may be an essential process during metastasis and should appropriately stimulate further investigations of EMT in many laboratories.