Immunotherapy in colorectal cancer (CRC) has largely focused on microsatellite instability (MSI) tumors, based on the assumption that high mutational burden drives immunogenicity. However, most CRCs are microsatellite-stable (MSS) and remain unresponsive to checkpoint blockade. Using proteogenomic profiling of 26 primary CRC tumors, we identified 115,292 MHC-I–associated peptides across 61 HLA alleles, yielding 196 tumor-associated antigens (TAAs) and 70 aberrantly expressed tumor-specific antigens (aeTSAs).