UNLABELLED: To overcome the paucity of known tumor-specific surface antigens in pediatric high-grade glioma (pHGG), we contrasted splicing patterns in pHGGs and normal brain samples. Among alternative splicing events affecting extracellular protein domains, the most pervasive alteration was the skipping of ≤30 nucleotide-long microexons. Several of these skipped microexons mapped to L1-IgCAM family members, such as STATEMENT OF SIGNIFICANCE: Existing targets for chimeric antigen receptors (CAR)-armed T cells are often shared by CNS tumors and normal tissues, creating the potential for on-target/off-tumor toxicities. Here we demonstrate that in CNS tumors of glial origin, cell adhesion molecules have alternatively spliced proteoforms, which could be targeted by highly selective therapeutic antibodies.