Cell adhesion molecules (CAMs) are glycoproteins expressed on the surface of cell membranes. In normal cells, CAMs participate in a variety of biological processes including cell proliferation, migration and differentiation. In tumor cells, CAMs have been reported to function as oncogenes or tumor suppressors, in signal transduction1-4 and as regulators of tumor progression and metastasis.5 CAMs interact directly with each other as well as with multiple intracellular proteins and extracellular matrix components. Relevant to this review, direct and indirect interactions of CAMs with the extracellular matrix and with the actin cytoskeletal network control cell motility. Cell motility, in turn, regulates the migra tory and invasive potential, i.e., the metastatic potential, of tumor cells. The question to be addressed in this review is whether CAM-mediated molecular interactions that regulate metastasis represent potential therapeutic targets for metastatic neuroblastoma. ©2009 Landes Bioscience.