Mice lacking DNA ligase IV (Lig4), a major component of nonhomologous end-joining, die in utero due to massive neuronal death. This embryonic lethality and neuronal death is rescued by p53 deficiency indicating that neuronal apoptosis resulting from DNA breaks during neurogenesis is p53 dependent. All mice lacking both Lig4 and p53 developed medulloblastoma by 9 weeks of age, suggesting that there is a strong link between genomic instability and medulloblastoma formation. The H/E figure shows a typical example of Lig4^-/-p53^-/- medulloblastoma present in the molecular layer of the cerebellum. There are also other tumor foci present in the molecular layer between the lobulus centralis and culmen. The mouse medulloblastoma has typical cytological features of human medulloblastoma, such as densely packed cells with a high nuclear:cytoplasmic ratio and immunoreactivity for neuronal marker. For details, see the article by Y. Lee et al. on page 6395 of this issue.