RUNX transcription factors function as scaffolds for interaction with various coregulatory proteins during developmental processes such as hematopoiesis, neurogenesis, and osteogenesis. The current view places RUNX proteins within the TGF‐β signaling pathway, although each one exhibits cell‐ and tissue‐specific functions. In the case of RUNX3, recent data have suggested its function as a tumor suppressor factor and highlighted its involvement in immune cell differentiation and activation. The molecular mechanisms for the pleiotropic effects of Runx3 deficiency are not completely understood. The present article will summarize the known functional activities of RUNX3, emphasizing its role in myeloid cell gene expression and its potential contribution to the migratory and adhesive capabilities of this cell lineage. J. Cell. Biochem. 98: 744–756, 2006. © 2006 Wiley‐Liss, Inc.