Expression of activated mutants of c-Src in epithelial cells can induce tumorigenicity. In addition to such oncogenic transformation, the cells undergo a dramatic morphological transformation: cell-cell contacts are disrupted, spreading on extracellular matrix proteins is suppressed, actin stress fibers and focal contacts are lost, and podosomes are formed. We have previously shown that integrin avß3 strongly supports Src-mediated oncogenic transformation through an interaction at the ß3 cytoplasmic tail. Our current findings demonstrate that this interaction does not affect Src-mediated morphological alterations, thus separating oncogenic- from morphological transformation. Moreover, ß1 and ß3 integrins differently affect the various aspects of Src-induced morphological transformation. High levels of ß3, but not ß1 integrins can prevent Src-induced cell rounding while stress fiber disassembly and podosome formation still occur. Studies using chimeric integrin subunits demonstrate that this protection requires the ß3 extracellular domain. Finally, like tumor formation, podosome assembly occurs independent of ß3 phosphorylation. Instead phosphorylation of ß1 is required to suppress Rho-mediated contractility in order to assemble podosomes. Thus, integrins regulate Src-mediated oncogenic transformation and various aspects of morphological transformation through dissociable pathways.