Purpose: Primary central nervous system lymphoma (PCNSL) accounts for approximately 3% of all primary brain tumors and 1% of all non-Hodgkin lymphomas. Detection of systemic spread of PCNSL, although rare (4%), is very important since therapy is usually modified. Contrast-enhanced computed tomography (CT) is commonly used for systemic staging of PCNSL. No previous case report is available in the published literature elaborating the potential contribution of F-18 FDG PET in systemic staging of PCNSL. The purpose of this case report was to document the potential usefulness of F-18 FDG-PET in the detection of occult systemic involvement in PCNSL., Materials and Methods: A 50-year-old, immunocompetent, male patient completed successful treatment of PCNSL. As part of a routine pretransplant evaluation he had an F-18 FDG PET coregistered with CT (PET-CT). The PET-CT results were then compared with those of contrast-enhanced CT of the chest, abdomen, and pelvis., Results: The PET-CT examination detected multiple sites of extranodal systemic disease that were not seen in the contrast-enhanced CT of the chest, abdomen, and pelvis (both studies were performed within 24 hours of each other). Percutaneous ultrasound guided biopsy confirmed the presence of systemic spread of PCNSL. The patient's subsequent therapy was modified to include rituximab with cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). A follow up PET-CT confirmed resolution of systemic spread., Conclusion: F-18 FDG PET coregistered to CT may be a useful examination in the detection and monitoring for systemic spread of the disease in PCNSL patients.