Malignant rhabdoid tumors (MRTs) are rare, aggressive cancers occuring in young children primarily through inactivation of the SNF5(INI1, SMARCB1) tumor suppressor gene. We and others have demonstrated that mice heterozygous for a Snf5 null allele develop MRTs with partial penetrance. We have also shown that Snf5 mice that lack expression of the pRb family, due to TgT121 transgene expression, develop MRTs with increased penetrance and decreased latency. Here, we report that altering the genetic background has substantial effects upon MRT development in Snf5 and TgT121;Snf5 mice, with a mixed F1 background resulting in increased latency and the appearance of brain tumors. We also report the establishment of the first mouse MRT cell lines that recapitulate many features of their human counterparts. Our studies provide further insight into the genetic influences on MRT development as well as provide valuable new cell culture and genetically engineered mouse models for the study of CNS-MRT etiology. WHATʼS NEW?: Malignant rhabdoid tumors (MRTs) are rare, extremely aggressive cancers occurring in young children primarily through inactivation of the SNF5 (INI1, SMARCB1) tumor suppressor gene. This study characterizes the first MRT cell lines derived from genetically engineered mouse models as well as the effects of genetic background on in vivo MRT development. These cell lines will provide critical new reagents for dissecting the mechanisms that drive the epigenetic instability found in these unique tumors as well as serve as biological models for testing novel drugs for the treatment of this aggressive disease.