A novel concept for the control of oncogenesis has been established for fibroblasts. Transformed fibroblasts are subject to intercellular induction of apoptosis by TGF-beta or FGF-triggered nontransformed neighboring cells. If this control system acts in vivo as efficiently as it does in vitro, tumor formation should require the establishment of resistance mechanisms directed against intercellular induction of apoptosis. In line with this hypothesis, ex vivo tumor cells have been recently shown to be resistant to intercellular induction of apoptosis, whereas cells transformed in vitro and not passaged in an organism were regularly sensitive. Based on the knowledge of signaling between transformed and nontransformed cells during intercellular induction of apoptosis, several possible mechanisms for resistance of tumor cells are summarized in this paper.