Background Primary gastrointestinal follicular lymphoma is a rare variant of follicular lymphoma. The most common location of involvement is the second portion of the duodenum and detection is often incidental during upper endoscopy. The clinical course is usually indolent. Dissemination is rare and transformation into high-grade lymphoma almost never occurs even without treatment. Histologically, diagnosis can be difficult, appearing as a benign lymphoid infiltrate prior to immunohistochemical staining. We present the case of a patient with a rare primary gastrointestinal follicular lymphoma. Case A 54-year-old Caucasian female previously healthy was referred for evaluation of intermittent epigastric pain associated with reflux. There were no fevers, chills or weight loss. Upper endoscopy performed at an outside facility was significant for a nodular duodenal mucosa in the bulb and second portion with biopsy showing atypical lymphoid infiltrate. A repeat upper endoscopy at our facility had identical endoscopic findings with extensive duodenal biopsy showing lymphoid infiltrate. A second pathologic opinion noted lymphoid nodules with small and large cells that were CD20 positive B-cells which co-expressed Bcl-2, Bcl-6 and CD10 consistent with follicular lymphoma. Staging position emission tomography scan showed no hypermetabolic areas and bone marrow biopsy showed no lymphoma but did note an incidental chronic lymphocytic leukemia. Discussion Follicular lymphoma comprises only 1-3% of primary gastrointestinal lymphomas. When follicular lymphoma does involve the gastrointestinal tract, the duodenum is most often affected (89% of cases). Endoscopically, follicular lymphoma usually manifests as multiple white nodules < 10 mm in size. The diagnosis of follicular lymphoma requires identification of a neoplastic infiltrate forming nodular follicles. The majority of primary gastrointestinal follicular lymphomas express Bcl-2 and CD-20. Treatment options include: watch and wait, radiation, rituximab monotherapy or chemotherapy with or without radiation. Conclusions Primary gastrointestinal follicular lymphoma is a rare, indolent neoplasm that may appear as a benign lymphoid infiltrate. Immunohistochemical staining is critical in making the diagnosis particularly in the setting of atypical lymphoid infiltrates that are nodular. In patients with localized disease, clinical outcomes are excellent even without therapy.Figure: Follicular lymphoma duodenal bulb.