A case is described of a patient who presented with multifocal neurologic disease compatible with a diagnosis of multiple sclerosis. The predominance of cognitive abnormality was unusual in this case. It was not until the patient's rapid clinical deterioration and radiographic findings mandated surgical intervention that a disseminated tumor involving the leptomeninges was identified and a diagnosis of primary CNS lymphoma was made. Postmortem examination confirmed the diagnosis of primary CNS lymphoma, and the classical pathologic findings of multiple sclerosis were also seen. This report illustrates interesting parallels in the clinical differentiation of these two diseases.