A 67-year-old man was referred for a whole-body F-18 fluorodeoxyglucose (FDG) positron emission tomographic (PET) scan for evaluation of possible lymphoma. At the time of the scan, he had fever, weight loss, diaphoresis, and pancytopenia. A computed tomographic (CT) scan of the abdomen showed splenomegaly and an enlarged tortuous venous structure, but findings of CT scans of the neck, chest, and pelvis were normal. An FDG-PET scan showed intense uptake in the spleen and in the enlarged veins that were seen on the CT scan. Lymphoma was ruled out by a standard diagnostic work-up, and the patient underwent splenectomy for symptomatic management. Histopathologic analysis at the time of surgery showed red pulp congestion with no significant fibrosis. No nodules or tumors were identified. Flow cytometric analysis revealed mixed T cells, polyclonal B cells, and natural killer cells, consistent with a reactive process with no evidence of tumor or hematopoietic disease. This case shows markedly increased FDG uptake in benign congestive splenomegaly.