The study investigates somatic mutations in histone H3 genes in paediatric diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem paediatric glioblastomas (non-BS-PGs). Whole genome sequencing of 7 DIPGs and targeted sequencing of 43 DIPGs and 36 non-BS-PGs revealed that 78% of DIPGs and 22% of non-BS-PGs contained p.K27M mutations in *H3F3A* or *HIST1H3B*, encoding histone H3.3 and H3.1, respectively. Additionally, 14% of non-BS-PGs had p.G34R mutations in *H3F3A*. These mutations were mutually exclusive and not observed in other tumour types or germline DNA, indicating they are somatic. The mutations are located in highly conserved regions of histone H3, which may affect chromatin structure and gene expression. The study suggests that these mutations confer a selective advantage in the context of developing brains, highlighting differences in gliomagenesis between children and adults.The study investigates somatic mutations in histone H3 genes in paediatric diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem paediatric glioblastomas (non-BS-PGs). Whole genome sequencing of 7 DIPGs and targeted sequencing of 43 DIPGs and 36 non-BS-PGs revealed that 78% of DIPGs and 22% of non-BS-PGs contained p.K27M mutations in *H3F3A* or *HIST1H3B*, encoding histone H3.3 and H3.1, respectively. Additionally, 14% of non-BS-PGs had p.G34R mutations in *H3F3A*. These mutations were mutually exclusive and not observed in other tumour types or germline DNA, indicating they are somatic. The mutations are located in highly conserved regions of histone H3, which may affect chromatin structure and gene expression. The study suggests that these mutations confer a selective advantage in the context of developing brains, highlighting differences in gliomagenesis between children and adults.