The relationship between chronic inflammatory conditions and malignancy is complex. We describe the clinical course of 2 patients with Crohn's disease (CD) in whom lymphoma was diagnosed after treatment with infliximab. The first patient was a 61-year-old man with a 30-year history of fistulizing CD in whom B-cell non-Hodgkin's lymphoma was diagnosed 9 months after treatment with infliximab. The second is a 29-year-old man with CD in whom nodular sclerosing Hodgkin's lymphoma was diagnosed 3 weeks after infusion with infliximab. The lymphoma presented with pleural effusions, mediastinal and cervical adenopathy, and no gastrointestinal lesion. We describe the implications of these cases for the use of immunomodulatory therapy in CD and the questionable association between CD and lymphoma.