Metastasis is the major cause of mortality and morbidity for patients with cancer. The high-mobility group protein 1(Y) [HMG-1(Y)] has a role in the transcription of many genes involved at different steps in the metastatic cascade and has been linked with cancer in human and animal models. This may represent a potential therapeutic target for patients. The following review summarizes and critically appraises the evidence for the role of HMG-1(Y) in metastasis. J. Surg. Oncol. 2004;88:86–99. © 2004 Wiley-Liss, Inc.