AbstractTumor‐initiating cells (TICs) with stem‐like cell properties initiate and sustain progressive growth, resulting in a heterogeneous tumor mass. The survival and growth of tumors rely on the development of a vasculature to provide nutrients and oxygen. Crosstalk between TICs and vascularization may be one of the central players in the initiation, long‐term maintenance, and progression of tumors. This review surveys current evidence concerning the crosstalk that occurs in tumor/stromal interactions, including genetic change, vascular niche, hypoxia, and dormancy of tumors. A better understanding of this crosstalk might help provide the basis for developing more effective therapeutic drug targets. Pediatr Blood Cancer 2011;56:335–340. © 2010 Wiley‐Liss, Inc.