The term mitotic catastrophe (MC) was coined to describe the mammalian cell death caused by aberrant mitosis. MC occurs with features that are fundamentally different from those typifying other forms of cell death, including apoptosis. We report here for the first time that the Rac-activating toxin CNF1 interferes with the occurrence of MC and leads to aneuploidy and multinucleation. This seems to be in line with the anti-apoptotic activity of the toxin and consistent with the hypothesis that points at CNF1 as a toxin bearing a carcinogenic potential.