Posterior reversible leukoencephalopathy (PRLE) is a neurological disorder caused by a variety of pathological conditions such as high doses or long-term low-doses of immunosuppressive therapy. PRLE associated with methotrexate (MTX) is well known but it was rarely observed in adult patients submitted to long-term low-dose administration via the oral route. Here we report the case of a patient affected by psoriasis, treated by chronic oral low-dose of MTX, who presented with limb ideomotor apraxia. Magnetic resonance (MRI) of the brain showed, on T2-weighted images, a diffuse hyperintensity involving bilaterally the white matter of the occipital, parietal and frontal lobes. MTX treatment was stopped and, at the 6-month follow-up, the neuropsychological performances was improved. Two years later, the neuropsychological profile was normal and MRI showed a regression of the white matter abnormalities.