Primary central nervous system lymphoma (PCNSL) can be confused with multiple sclerosis (MS) in patients who present with neurological dysfunction, a non-enhancing periventricular lesion, and CSF pleocytosis. Administration of corticosteroid causes clinical improvement and regression of PCNSL in some patients which may be interpreted as a steroid-induced remission from an exacerbation of MS. Sustained clinical dependence upon corticosteroid is unusual in MS, and should lead to consideration of PCNSL. Repeat CSF examination and gadolinium-enhanced MRI scan obtained off corticosteroid should differentiate between the two diagnostic possibilities.