Medulloblastoma (MB) is the most common malignant brain tumor of childhood and is reported to have a low mutational burden. However, in this study, we identified nine MBs with high mutational burden by next generation sequencing. Of them, two had canonical mutations in the POLE proof-reading domain, where a large proportion of mutations in these tumor genomes contributed to signature 10. We report very rare incidences of hypermutation in MB and mechanisms driving mutagenesis. Strikingly, of the four known molecular subgroups in MB—-SHH, WNT, Group 3, and Group 4—both the POLE-mutated MBs belonged to the SHH subgroup.