Exitrons (exonic introns: defined as cryptic introns within protein coding exons) represent a non-canonical form of RNA splicing that alters protein coding genes. While exitrons are introns, they display many exon-like properties. Alternative splicing events involving exitrons add to the complexity of the proteome and thus enhance phenotypic diversity. Recent observations of exitron splicing occurring in cancer genes suggest that exitron-spliced isoforms may contribute to cancer development. Furthermore, tumor-specific exitron splicing junctions resulting in internal deletions or frameshifts may generate immunogenic peptides (i.e., neoantigens) that could form a basis for developing cancer vaccines or T-cell therapeutic targets. In this talk, I will introduce our recent in-depth analyses of exitron splicing events among numerous cancer patient samples. Our findings highlight the importance of considering exitron splicing alterations when nominating cancer driver events and immunogenic neoantigens.