Here, we demonstrate that A3A alone is capable of triggering similarly robust tumor phenotypes 6 months p.i. and, remarkably, that tumor formation becomes evident as early as 6–8 weeks p.i. A3A-driven tumorigenesis is completely dependent on functionality of the catalytic glutamate residue (E72), which is essential for deprotonation of water and hydrolytic attack of target cytosine nucleobases. Here, APOBEC3A is linked to neoplasm.