Background <p>Medulloblastoma is similar to other common tumors in the posterior cranial fossa of children in terms of the onset and clinical manifestations. Still, its main treatment methods, surgical methods and prognosis are quite different. Therefore, there is an urgent need for finding biomarkers for differential diagnosis.</p> Purpose <p>The purpose of this study was to identify new lipids and differential metabolic pathways by analyzing the significantly different lipids present in the plasma of children with medulloblastoma in comparison to those with other intracranial tumors.</p> Methods <p>In this study, 35 patients with medulloblastoma and 32 matched controls were enrolled. Plasma samples and medical records were collected, and untargeted lipidomics analyses were performed using UHPLC-MS/MS. </p> Results <p>A total of 97 differential lipids in the plasma of children with medulloblastoma were identified. Seven differential lipids could be potentially useful in medulloblastoma detection and a diagnostic model was established. The metabolic pathway analysis showed that there were significant differences in patients with medulloblastoma in terms of glycerophospholipid metabolism metabolism, sphingolipid metabolism and linoleic acid metabolism pathways. </p> Conclusion <p>The difference in plasma lipid markers between medulloblastoma and other intracranial tumors screened in this study may be useful to support and improve the differential diagnosis of medulloblastoma in children.</p>