<h4>Introduction</h4>This study aimed to elucidate the function of NOTCH3 in pan-cancer and CRC progression, its impact on the tumor immune microenvironment, and its value as a therapeutic target and predictive biomarker.<h4>Methods</h4>We performed a multi-omics analysis of NOTCH3 alterations (expression, mutation, copy number variation, methylation) using data from The Cancer Genome Atlas (TCGA). This evidence concerns the gene NOTCH3 and neoplasm.