Although identification of the Ewing sarcoma breakpoint region 1:cAMP response element binding protein 1 (EWSR1:CREB1) fusion gene by reverse transcription-polymerase chain reaction (RT-PCR) is the most reliable method for diagnosis, in practice, PPMS is often diagnosed when EWSR1 gene rearrangement is found by fluorescence in situ hybridization (FISH) and the histological features and immunostaining results are consistent. Here, EWSR1 is linked to primary progressive multiple sclerosis.