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The correct diagnosis of a patient presenting with a solid pancreatic mass requires a careful diagnostic work-up, since many differential diagnoses are possible that completely alter the following treatments. In our chapter, we have discussed the clinical approach to the problem in a sort of diagnostic flow-chart. Firstly, we analysed the different potential presentations of a solid pancreatic mass, which can be both asymptomatic or symptomatic, and the differential diagnosis based on the symptoms of presentation. Then we focused on the various imaging techniques commonly used in the diagnostic work-up, stressing on the different presentations according to the type of disease, and the operative procedures that can supplement this part. Lastly, we discussed the best diagnostic work up that should be followed to fully understand the characteristics of each disease, which is of paramount importance to choose the adequate treatment plan, with special attention to pancreatic adenocarcinoma and its many treatment strategies such as chemotherapy, surgery, or medical therapy. In patients presenting with a solid pancreatic mass it is crucial to reach a definitive diagnosis using a well determined diagnostic work-up to better characterize the lesion, since the best treatment varies widely according not only to the type of disease but also to its features.