Transplant oncology defines any application of transplant medicine and surgery aimed at improving cancer patients' survival and/or quality of life. In practice, liver transplantation for selected hepato-biliary cancers is the only solid organ transplant with demonstrated efficacy in curing cancer. Four are the proposed future contributions of transplant oncology in hepato-biliary cancer (4-e). 1. evolutionary approach to cancer care that includes liver transplantation; 2. elucidation of self and non-self recognition systems, by linking tumor and transplant immunology; 3. exploration of innovative endpoints both in clinical and experimental settings taking advantage from the access to the entire liver explant; 4. extension of surgical limitation in the multidisciplinary approach to hepato-biliary oncology. The aim of this review is to define the principles of transplant oncology that may be applied to hepato-biliary cancer treatment and research, attempting to balance current evidences with future opportunities.