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We report a psoriasis patient who presented with progressive neurologic dysfunction and seizures after 2.5 years of fumarate therapy. Despite absolute lymphocyte counts remaining between 500\u20101000\/mm<jats:sup>3<\/jats:sup>, his CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T\u2010cell counts were markedly low. MRI showed right hemispheric and brainstem lesions and JC virus DNA was undetectable in his cerebrospinal fluid. Brain biopsy revealed typical features of PML as well as JC virus\u2010infected neurons. Clinicians should consider PML in the differential diagnosis of fumarate\u2010treated patients presenting with brain lesions or seizures even in the absence of severe lymphocytopenia. 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