The in vitro organoid model is a major technological breakthrough that has been established as an important tool in many basic biological and clinical applications. This near-physiological 3D culture system accurately models various biological processes, including tissue renewal, stem cell/niche functions and tissue responses to drugs, mutations or damage. Organoids have the potential value of being an accurate model for disease predictions or drug screening applications and to identify the ideal treatment for that patient. Carcinogenesis can be modeled by mutating specific cancer genes in wild-type organoids; and patient-derived organoids provide an important resource in the development of personalized cancer treatment. Organoids from cancer patients could be used to identify the ideal treatment for a specific patient by growing matched healthy and diseased organoids from human cancer patients which additionally enables clinical screens for drug combinations. Organoids could also provide autologous cells or-in the future-tissue for transplantation. In this review, we discuss the current advances, challenges and potential applications of this technique in gastrointestinal neoplasms.