CD146 is a cell adhesion molecule (CAM) that is primarily expressed at the intercellular junction of endothelial cells. CD146 was originally identified as a tumor marker for melanoma (MCAM) due to its existence only in melanoma but not in the corresponding normal counterpart. However CD146 is not just a CAM for the inter-cellular and cell-matrix adhesion. Recent evidence indicates that CD146 is actively involved in miscellaneous processes, such as development, signaling transduction, cell migration, mesenchymal stem cells differentiation, angiogenesis and immune response. CD146 has increasingly become an important molecule, especially identified as a novel bio-marker for angiogenesis and for cancer. Here we have reviewed the dynamic research of CD146, particularly newly identified functions and the underlying mechanisms of CD146. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.