Variant Creutzfeldt-Jakob disease (vCJD) is a novel human prion disease that results from exposure to the bovine spongiform encephalopathy (BSE) agent, probably by the oral route. The pathological features of vCJD are unique, with extensive involvement of lymphoid tissues in addition to the central nervous system. This article reviews the histopathology and biochemistry of vCJD, emphasising diagnostic features and indicating several areas of active research. The widespread distribution of infectivity in lymphoid tissues in vCJD has lead to concerns over the possibility of iatrogenic disease transmission by contaminate surgical instruments, or by blood transfusion. vCJD has so far only occurred in individuals within a genetic subset defined by the natural polymorphism at codon 129 in the prion protein gene. It remains uncertain if this disease will occur in other genetic subgroups within the population. Continuing surveillance of vCJD in the UK and other countries in which BSE has been identified will be necessary for future estimations of disease numbers worldwide.