Background Obstructive jaundice caused by primary duodenal lymphoma is a rare disease. Case presentation We reported a 59-year-old man who underwent endoscopic ultrasonography for obstructive jaundice and found a duodenal papilla tumor. Light microscopy revealed a non-Hodgkin's lymphoma. Immunohistochemical staining showed that the tumor was aggressive B-cell lymphoma. We carried out molecular targeted therapy combined with CHOP regimen chemotherapy. Conclusion Surgery plays an important role in resolving obstructive jaundice when accurate histological diagnosis cannot be made. After diagnosis, chemotherapy should play a central role in treatment.