The aim of this study was to investigate the relationship between clinical course and diffusion-weighted MRI (DWI) findings in sporadic Creutzfeldt-Jakob Disease (sCJD). We reviewed clinical records and MRI examination in nine probable sCJD. According to hyperintense signal distribution on DWI, the patients were classified into two groups with cortical ribbon plus basal ganglia hyperintensity (6/9) and with only increased cortical signals (3/9). Clinical features including quadriparesis (3/6), akinetic mutism (2/6), and dysphasia (2/6), which were usually observed in the more advanced stage of CJD, were noted only in patients with cortical ribbon plus basal ganglia hyperintensity at the time of initial DWI examination. The patients with the cortical plus basal ganglia hyperintensity (6.4+/-1.7 weeks) had a shorter interval from symptom onset to akinetic mutism than those with only cortical ribbon hyperintensity (26.0+/-22.5 weeks) (p=0.02). These findings suggest that DWI may predict the clinical course of CJD.