In the variant form of Creutzfeldt-Jakob disease (vCJD), ‘florid’ deposits of the protease resistant form of prion protein (PrPsc) were aggregated around the cerebral blood vessels suggesting the possibility that prions may spread into the brain via the cerebral micro circulation. The objective of the present study was to determine whether the pathology was spatially related to blood vessels in cases of sporadic CJD (sCJD), a disease without an iatrogenic etiology, and therefore, less likely to be caused by hematogenous spread. Hence, the spatial correlations between the vacuolation (‘spongiform change’), PrPsc deposits, and the blood vessels were studied in immunolabeled sections of the cerebral cortex and cerebellum in eleven cases of the common M/M1 subtype of sCJD. Both the vacuolation and the PrPsc deposits were spatially correlated with the blood vessels; the PrPsc deposits being more focally distributed around the vessels than the vacuoles. The frequency of positive spatial correlations was similar in the different gyri of the cerebral cortex, in the upper and lower cortical laminae, and in the molecular layer of the cerebellum. It is hypothesised that the spatial correlation is attributable to factors associated with the blood vessels which promote the aggregation of PrPsc to form deposits rather than representing the hematogenous spread of the disease. The aggregated form of PrPsc then enhances cell death and may encourages the development of vacuolation in the vicinity of the blood vessels.