Leptomeningeal metastasis (LM) is a rare but increasingly common condition in which malignant cells migrate to the meninges. The gold standard for diagnosing LM is detection of cancer cells in the cerebrospinal fluid (CSF). Contrast enhanced-magnetic resonance imaging (CE-MRI) is also used to diagnose LM. We describe a case of LM in which CE-MRI of the neuroaxis was initially negative for meningeal enhancement but F-18 fluorodeoxyglucose positron-emission tomography/computed tomography (F-18 FDG PET/CT) revealed hypermetabolism within the lumbar spinal canal. Positive F-18 FDG PET findings have rarely been reported in LM and, to our knowledge, have never been reported in the context of initially negative CE-MRI scanning of the neuroaxis. F-18 FDG PET/CT may represent an alternative modality for diagnosing LM in patients who are unable to undergo CE-MRI and/or LP or in patients for whom initial CE-MRI and/or LP are negative for LM.