The Yaroslavl region is an endemic area for Lyme disease (LD) with one of the highest levels of morbidity in Russia. Chronic neuroborreliosis can mimic multiple sclerosis and cause considerable difficulties in differential diagnosis. A comparative clinical-instrumental analysis of patients with definite multiple sclerosis (n=65) and chronic borrelial encephalomyelitis (n=11) was carried out. The key differential-diagnostic features of multiple sclerosis and borrelial encephalomyelitis were specified. Migrating erythema and tick's bite in the anamnesis, combined with lesions of the central and peripheral nervous systems, the absence of retrobulbar neuritis in the anamnesis, artralgia and myalgia, the high blood sedimentation rate were not characteristic of multiple sclerosis. A patient with abovementioned findings should be tested for the presence of antibodies to Borrelia burgdorferi in the blood serum and, if necessary, in the cerebrospinal fluid to exclude the diagnosis of Lime disease.