Gastrointestinal cancers represent a challenge for public health, especially due to their elevated incidence and poor prognosis. They have a well-known natural history, and endoscopic/surgical treatment options are available if diagnosed at early stages. For this reason, secondary prevention strategies consisting of mass or targeted screening aimed at detecting and removing precancerous lesions and early cancer have been implemented worldwide and have proven to reduce mortality and morbidity rates significantly. This chapter outlines the epidemiological profile, carcinogenetic process, precursor lesions, and secondary prevention strategies of digestive tract tumors, namely, esophageal, gastric, and colorectal cancer, and neuroendocrine neoplasms.