Central nervous system (CNS) involvement by mycosis fungoides (MF) is rare and is usually seen in advanced stages with lymph node or visceral involvement. We describe a patient with advanced stage MF in large-cell transformation who presented with profound hearing loss after chemotherapy. Despite an initial differential diagnosis of vincristine-related neurotoxicity based on clinical, audiometric, and MRI investigations, CSF examination revealed lymphomatous leptomeningeal involvement. This case illustrates the importance of an awareness of the possibility of CNS involvement by MF and underlines the need for a complete neurologic evaluation including CSF examination in a patient with underlying MF who presents with a new neurological problem.