Background: Due to improvements in diagnosis, the better outcomes of oncological patients and the increase in the average age, the incidence of synchronous tumours is likely to increase. Aim: To reflect on the challenges of a case with multiple integrated diagnostic and therapeutic approaches and to bring to consideration the increasing prevalence of similar situations. Case Presentation: In this clinical case, the authors describe the evolution of an asymptomatic patient with several synchronous tumours (a GEJ primary adenocarcinoma, a low grade urothelial carcinoma in situ, a localized squamous cell lung carcinoma and 2 IPMNs). Conclusion: The challenge of this case lies in the difficult diagnostic approach, the assembly of a multidisciplinary and time-sensitive treatment plan and the individualized follow-up, due to lack of guidelines. More research is needed in this area.