Gastrointestinal malignancies represent a healthcare concern worldwide. In recent decades, several innovations in gastrointestinal endoscopy have radically changed approaches to digestive neoplasms. As a result, many preneoplastic or neoplastic lesions of the digestive tract are now amenable to endoscopic resection through innovative techniques, avoiding the need for surgery. These techniques include endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), endoscopic full-thickness resection (EFTR), and others. Moreover, endoscopy has several applications in the palliative treatment of gastrointestinal cancers that are unfit for curative therapies. In addition, for cancers susceptible to population screening, such as colorectal cancer, endoscopy has a crucial role in screening and surveillance, contributing to the reduction in cancer incidence and mortality all over the world. Finally, beyond luminal endoscopy, retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) play a crucial role in the approach to biliopancreatic neoplasms. All these application areas place endoscopy in a leading role in the prevention, diagnosis, management, and follow-up of many gastrointestinal malignancies. This Special Issue aims to summarize all the main applications of endoscopy for digestive neoplasms, as well as the evidence from the literature supporting the effectiveness and safety of the main endoscopic techniques for the curative or palliative treatment of gastrointestinal cancers.