Multiple sclerosis (MS) is very similar to the Sjögren's syndrome (SS) by its clinical presentations. Features found in common between the two disorders include symptoms of lesions of the brain, spinal cord and optic tract, the detection of autoantibodies, such as antinuclear, anti-Ro, anti-La and the prevalence of MRI abnormalities such as periventricular and subcortical lesions. Almost all symptoms found in patients with the CNS-SS involvement described above could be attributed to the concomitant presence of MS. Therefore, the differential diagnosis of these diseases is difficult. The paper addresses clinical and biological presentations of similarity of and differences between MS and SS in the diagnostic aspect.