The discovery of IDH1 and IDH2 mutations in the large majority of WHO grade II and grade III glioma represented a real breakthrough in the understanding of gliomagenesis: it appeared evident that mutant IDH proteins acquire a constitutive neomorphic enzymatic activity, contributing to generate, in the gliomas in which they are mutated, an aberrant pattern of DNA and histone methylation, resulting in hypermethylation of CpG islands, commonly known as “glioma CpG-island methylation phenotype”. Here, IDH2 is linked to central nervous system cancer.