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Diffuse Large B-Cell Lymphoma (DLBCL) is the most common histological subtype of Non-Hodgkin's Lymphoma (NHL). Primary retroperitoneal DLBCL is uncommon and has seldom been reported. Extrinsic compression of the duodenum due to lesions originating from the retroperitoneum is also rare. We present a case of a 39-year-old man who presented with inability to tolerate oral intake, abdominal pain, an upper abdominal mass and postprandial bilious vomiting caused by a large DLBCL arising from the retroperitoneum causing extrinsic compression of the duodenum. The cause of compression was initially presumed to be a neoplasm arising from the uncinate process of the pancreas or duodenum because of its proximity to the uncinate process and apparent widening of the C loop of duodenum. Repeat Computed Tomography (CT) scans were obtained because of the rapid increase in the size of the mass, normal levels of tumour markers such as Cancer Antigen (CA) 19-9, Carcinoembryonic Antigen (CEA) and no evidence of jaundice in spite of the large size of the mass. It revealed encasement of the uncinate process of pancreas with no involvement of parenchyma of the pancreas, thereby mimicking a pancreatic tumour. The neoplastic lymphoid cells were positive for Leukocyte Common Antigen (LCA), Cluster of Differentiation (CD)20, CD10, B-cell Lymphoma 2 (Bcl-2) and were negative for Creatine Kinase (CK), CD23, CD30, Anaplastic Lymphoma Kinase (ALK) and cyclin D1, D3 and D5. The Ki67 proliferative index was greater than 95%. Retroperitoneal DLBCL although rare should be considered in cases of duodenal obstruction. [ABSTRACT FROM AUTHOR]