Tumefactive demyelinating (TDL) lesions are focal zones of demyelination in the central nervous system and they often mimic the neuroimaging features of an intraxial neoplasm. In this report we describe the clinical, neuroimaging and neuropathological features of six cases of TDL. Only in two patients the neuroimaging features in MRI (magnetic resonance imaging) scans were suggestive of TDL while in the other four cases a diagnosis of glioma was suggested. In order to establish a confirmatory diagnosis neuronavigation/stereotactic biopsy was undertaken and the diagnosis of TDL was established in all six cases at histopathology. Two out of six patients did not respond to the conventional corticosteroid therapy and they were treated with plasma exchange. It is being concluded that neuronavigation biopsy, though provide only a small amount of tissue, and is extremely useful in making the diagnosis of TDL.