The presence of tumefactive lesions on magnetic resonance imaging (MRI) in multiple sclerosis (MS) patients can cause diagnostic difficulties. It requires differential diagnosis between tumefactive demyelinating lesion (TDL) and the coexistence of neoplasm; it also implies further management. The precise assessment of such lesions at the first clinical manifestation of the disease is particularly important. We present three cases of MS presenting with tumour-like lesions of the brain. Based on serial MRI studies, stereotactic biopsy and the response to treatment with corticosteroids, the diagnosis of TDL was established in every case.