Central nervous system (CNS) is a rare site of involvement by non-Hodgkin lymphoma (NHL). Therapeutic approach for primary and secondary CNS NHL is different and remains challenging. Therefore imaging data are essential at staging to discriminate these 2 clinical entities and during follow-up to assess therapy response. The adjunct role of positron emission tomography using F-18 fluorodeoxyglucose to morphologic imaging is still undefined. We report 2 didactic cases of primary and secondary CNS NHL assessed by F-18 fluorodeoxyglucose positron emission tomography. Metabolic imaging seems to be complementary to conventional imaging techniques for the extent-of-disease evaluation and therapy monitoring of CNS lesions.