Multiple sclerosis (MS) is one of the most common diseases of the central nervous system. Up to now, there is no pathognomonic test to ascertain the diagnosis and in 10 to 15% of MS cases there are problems in differential diagnosis. We report 15 bioptically diagnosed MS cases with atypical clinical, C.S.F. and neuroradiological findings. In each case the diagnosis of MS was made by CT/MRI-stereotactic brain biopsy. Neoplastic and other non-tumorous lesions could be excluded. Indications for and significance of stereotactic brain biopsy in atypical cases of MS are discussed.