While international consensus and the 2021 WHO classification recognize multiple molecular medulloblastoma subgroups, these are difficult to identify in current clinical practice. As a result, biology driven risk stratification and therapy assignment for medulloblastoma constitutes a major challenge. Here, we report mass spectrometry analysis of clinical samples as a method for medulloblastoma subgroup discovery and identify MYC immunohistochemistry (IHC) as a clinically tractable method for improved risk stratification.