Mouse papillomavirus (MmuPV1) is the first papillomavirus known to infect laboratory mice, making it an irreplaceable tool for research on papillomaviruses. Despite wide use, standardized techniques for conducting MmuPV1 animal research are lacking. In this report, we describe an unexpected MmuPV1 outbreak causing recurrent papillomatosis in a specific pathogen-free animal research facility. The infected mice displayed characteristic papillomatosis lesions from the muzzles, tails, and feet with histological signs including anisocytosis, epithelial dysplasia, and typical koilocytosis. Etiology studies showed that the papilloma tissues exhibited MmuPV1 infection with expression of viral early and late genes detected by RNA-ISH using MmuPV1 antisense probe to viral E6E7 region and antisense probe to viral L1 region. The viral L1 protein was detected by an anti-MmuPV1 L1 antibody. PCR amplification and cloning of the entire viral genome showed that the origin of the outbreak virus, named MmuPV1 Bethesda strain (GenBank Acc. No. PX123224), could be traced to the MmuPV1 virus previously used in studies at the same facility. Our data indicate that MmuPV1 could exist in a contaminated environment for a long period of time, and a standardized international animal protocol discussing how to handle MmuPV1 studies is urgently needed.