Diagnostic splenectomy is frequently performed in patients with suspected or known lymphoma. We evaluated whether preoperative 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) results may correlate with splenic pathology. Of 165 patients undergoing splenectomy at the Weill Cornell Medical Centre/New York Presbyterian Hospital from 2004 to 2006, 10 were identified as being performed to evaluate known or suspected lymphoma and included a pre-splenectomy FDG-PET scan. The scans were assigned to low, intermediate or high splenic metabolic activity based on standardized uptake values (SUV). Low activity was associated with benign findings or mantle cell lymphoma at splenectomy, intermediate activity with marginal zone lymphoma and high activity with DLBCL. This comprises the largest pathologically confirmed series of cases to evaluate splenic FDG-PET uptake in suspected or known lymphoma. Low splenic SUV appears less likely to be associated with splenic involvement of lymphoma; intermediate and high values suggest presence of lymphoma. Our findings support a potential role for preoperative FDG-PET in consideration of the need for splenectomy in these settings.