Spleen tyrosine kinase (Syk) was thought to be a hematopoietic cell-specific signaling molecule and plays an essential role in maturation of lymphocytes and activation of immune cells. Recent evidences show that it is also expressed by many non-hematopoietic cell types. Down-regulation of Syk expression was first observed during breast cancer progression, now its abnormal expression has also been detected in many other types of tumors. Syk could suppress tumorigenesis and metastasis, but the molecular mechanism remains unknown. Promoter hypermethylation is one of the mechanisms that lead to silencing of Syk gene. Increasing clinical evidences reveal a positive correlation of reduced Syk expression to increased risk for metastasis, and indicate that Syk may be a potential new tumor suppressor.