A human pancreatic cancer progression model from intraepithelial neoplasia to ductal adenocarcinoma has been proposed. This process has been modeled in the mouse by activation of mutant Kras in pancreatic progenitor cells. In this issue of Cancer Cell, present a modification of their initial model by introducing a mutant Tp53. This combination of genetic alterations leads to rapid and increased frequency of neoplasia progression resulting in pancreatic cancers that manifest chromosomal instability in the presence of apparent intact telomeres. These findings introduce Tp53-mediated chromosomal instability as key event for carcinoma development in this mouse model.