Several bat species live >20–40 years, suggesting that they possess efficient anti-aging and anti-cancer defenses. Here we investigate the requirements for malignant transformation in primary fibroblasts from four bat species Myotis lucifugus, Eptesicus fuscus, Eonycteris spelaea, and Artibeus jamaicensis – spanning the bat evolutionary tree and including the longest-lived genera. We show that bat fibroblasts do not undergo replicative senescence, express active telomerase, and show attenuated SIPs with dampened secretory phenotype. Unexpectedly, unlike other long-lived mammals, bat fibroblasts are readily transformed by two oncogenic “hits”: inactivation of p53 or pRb and activation of HRASG12V. Bat fibroblasts exhibit increased TP53 and MDM2 transcripts and elevated p53-dependent apoptosis. M. lucifugus shows a genomic duplication of TP53. We hypothesize that some bat species have evolved enhanced p53 activity as an additional anti-cancer strategy, similar to elephants. Further, the absence of unique cell-autonomous tumor suppressive mechanisms may suggest that in vivo bats may rely on enhanced immunosurveillance. Cancer incidence is rare in long-lived bats. Here the authors find that although bat fibroblasts express telomerase and require only two oncogenic hits for malignant transformation, bats may rely on elevated p53 signaling and enhanced immunosurveillance to prevent cancer.