Gastrointestinal (GI) cancer groups the cancers that affect the digestive system, being colorectum, stomach, and pancreas the most relevant types according to i) incidence, ii) inheritance, iii) their high impact on therapeutics, as target for a high number of trial drugs, and iv) latest advances in somatic-germline association studies (used as “cancer models”). Early GI cancer detection is a hallmark for a successful treatment, unfortunately most cases are diagnosed at an advanced stage when the prognosis is poor, and the treatment options are limited.Our understanding of cancer genetics and the omics has been greatly enhanced by the overwhelming revolution in sequencing technology in recent years. Comprehensive studies, including analyses of the genome, methylome, proteome and transcriptome, enables us to expand our understanding of the molecular pathogenesis of GI cancers.This Research Topic focuses on advances in genetic predisposition, novel biomarkers, genome methylation and molecular diagnosis on a set of GI cancers. specifically colorectum, stomach, and pancreatic cancer. With this collection of articles, we aim to provide the progress and emerging genetic, genomic, and molecular findings for GI cancers, and to resume their clinical utility to improve the diagnosis and treatment of these malignancies; as well as the early identification of individuals at risk for them. We also call for articles to discuss the utility of patient molecular profiling to predict the efficacy of drug therapies and to classify, definitively diagnose, and predict the prognosis on this set of GI cancers.