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To investigate CT features and differential diagnosis of pancreatic adenocarcinoma compared to other solid tumours arising in the periampullary area. One hundred and ninety-five patients with pathologically proven, solid periampullary tumours, including pancreatic adenocarcinoma (n = 98), neuroendocrine tumours (n = 52), gastrointestinal stromal tumours (n = 31), and solid pseudopapillary neoplasms (n = 14), underwent preoperative CT. Two radiologists reviewed CT features and rated the possibility of pancreatic adenocarcinoma. Statistically common findings for pancreatic adenocarcinoma included: patient age >50 years; ill-defined margin; completely solid mass; homogeneous enhancement; hypoenhancement on arterial and venous phases; atrophy; and duct dilatation. Statistically common findings for GIST included: heterogeneous enhancement; hyperenhancement on arterial and venous phases; rim enhancement; and prominent feeding arteries. The hyperenhancement on arterial and venous phases is statistically common in NET, and heterogeneous enhancement, hypoenhancement on the arterial and venous phases are statistically common in SPN. Diagnostic performance of CT for differentiating pancreatic adenocarcinomas from other solid periampullary tumours was 0.962 and 0.977 with excellent interobserver agreement (κ = 0.824). CT is useful not only for differentiating pancreatic adenocarcinoma form other solid tumours but also for differentiating between other solid tumours, including NET, SPN, and GIST, arising in the periampullary area. • Periampullary tumours arise within 2 cm of major duodenal papilla. • Many mass-forming periampullary tumours can be completely removed by minimal surgery. • Accurate differentiation of pancreatic adenocarcinoma from other solid tumours is important. • CT is useful for differentiating pancreatic adenocarcinoma from other solid tumours. • CT is useful for characterization of periampullary tumours other than adenocarcinomas.