This study was aimed at investigating the value of MRI in the diagnosis of multiple sclerosis. In the Multiple Sclerosis Center of our University, we sorted out of the patients submitted to CSF and MR examinations, only those with clinically unquestionable multiple sclerosis, white matter abnormalities at MRI and normal CSF examination. These 21 patients were submitted to CSF and MRI examinations which were repeated whenever required if image quality was technically suboptimal; a variety of screening tests for different diseases mimicking multiple sclerosis were also performed. In 4 patients with white matter abnormalities at MRI which were considered atypical for multiple sclerosis, at image rereading and after laboratory tests the diagnosis were: coagulopathy, sarcoidosis, vasculitis and CNS lymphoma. In 2 cases with questionable white matter abnormalities at MRI, the final diagnosis were borreliosis and vasculitis. The remaining 15 patients had a diagnosis of multiple sclerosis in all but 3 cases in which subsequent clinical and laboratory examinations demonstrated the presence of vasculitis, embolism from interatrial septal aneurysm and mitochondrial disease. Our study suggests that in the patients with clinical findings of multiple sclerosis and disseminated MR lesions mimicking multiple sclerosis, but no CSF abnormalities, the classical clinical criteria may not be sufficiently specific and other diagnoses must therefore be excluded before making an "unquestionable" diagnosis of multiple sclerosis.