A 62‐year‐old man presented with abnormal behavior and cognitive impairment. Diffusion‐weighted images (DWI) obtained on MRI showed extensive hyperintense regions in the cerebral cortex and striatum. Myoclonus was recognized, and the patient died 1 month after the onset; his condition did not reach the akinetic mutism state. The brain weighed 1300 g and showed no apparent atrophy. Extensive spongiform changes were observed in the cerebral neocortex, striatum, thalamus and cerebellar cortex, but gliosis was mild or absent. Neuropil rarefaction and neuron loss were not apparent. Mild proliferation of anti‐ GFAP‐positive astrocytes was observed in the cerebral cortex, but unaffected regions were noted. Regions without spongiform changes and GFAP‐positive astrocytes included the hippocampal formation and subiculum. PrP immunostaining showed extensive diffuse synaptic‐type PrP deposition in the gray matter, including the hippocampal region, but it was also mild. PrP gene analysis revealed no mutation with methionine homozygosity at polymorphic codon 129. Western blot analysis of proteinase K‐resistant PrP indicated type 1 PrP^Sc. The clinicopathological findings of the present case confirm several hypotheses: (i) the earliest pathologic evidence observed by HE staining in CJD are spongiform changes; (ii) DWI hyperintense regions indicate these spongiform changes; and (iii) regions without spongiform changes, gliosis and proliferation of GFAP‐positive astrocytes, but with PrP deposition, exist in the early disease stage.