Liquid biopsy is increasingly recognized for tumor diagnosis and monitoring, and in medulloblastoma (MB) and other CNS tumors, it offers the potential to bypass invasive tissue collection. However, its application in clinical practice remains limited, in part because the optimal choice of biofluid is underexplored and may differ between tumor types. Here, we report mass spectrometry–based proteomic analysis of extracellular vesicles (EVs) from three matched cerebrospinal fluid (CSF) and blood plasma (BP) samples of MB patients, alongside healthy BP controls and MB cell lines.