Primary gastrointestinal lymphoma (PGL) is known to account for 40% of all extranodal non-Hodgkin's lymphomas (NHLs) and between 4% to 12% of all NHLs. The small intestine is the site of presentation in 20-30% of cases, with the terminal ileum usually involved. Duodenal localizations have always been thought to be rare, but are presently growing in incidence. We herein report on a case of Stage IV primary duodenal FCL, located to the second portion of the duodenum with concomitant minimal bone marrow involvement. The patient was frontline approached with a conservative combined modality treatment consisting of 4 weekly infusions of the chimeric human-murine IgG1 mono-clonal antibody against the B-cell surface antigen CD-20, Rituximab (375 mg/m2) and consolidation 3D conformal external beam radiotherapy up to a total dose of 36 Gy given into 20 fractions to the involved duodenal portion. Six years after treatment has been completed, the patient is free from disease with no treatment-related toxicity.