We analysed the epidemiological data and clinical features of patients with prion diseases that had been registered by the Creutzfeldt-Jakob Disease Surveillance Committee, Japan, over the past 10 years, since 1999. We obtained information on 1685 Japanese patients suspected as having prion diseases and judged that 1222 patients had prion diseases, consisting of definite (n=180, 14.7%) and probable (n=1029, 84.2%) cases, except for dura mater graft-associated Creutzfeldt-Jakob disease which also included possible cases (n=13, 1.1%). They were classified into 922 (75.5%) with sporadic Creutzfeldt-Jakob disease, 216 (17.7%) with genetic prion diseases, 81 (6.6%) with acquired prion diseases, including 80 cases of dura mater graft-associated Creutzfeldt-Jakob disease and one case of variant Creutzfeldt-Jakob disease, and three cases of unclassified Creutzfeldt-Jakob disease (0.2%). The annual incidence rate of prion disease ranged from 0.65 in 1999 to 1.10 in 2006, with an average of 0.85, similar to European countries. Although methionine homozygosity at codon 129 polymorphism of the prion protein gene was reported to be very common (93%) in the general Japanese population, sporadic Creutzfeldt-Jakob disease in Japan was significantly associated with codon 129 homozygosity (97.5%), as reported in western countries. In sporadic Creutzfeldt-Jakob disease, MM1 type (Parchi's classification) is the most common, as in western countries. Among atypical sporadic Creutzfeldt-Jakob disease cases, the MM2 type appeared most common, probably related to the very high proportion of methionine allele in the Japanese population. As for iatrogenic Creutzfeldt-Jakob disease, only dura mater graft-associated Creutzfeldt-Jakob disease cases were reported in Japan and, combined with the data from previous surveillance systems, the total number of dura mater graft-associated Creutzfeldt-Jakob disease was 138, comprising the majority of worldwide dura mater graft-associated Creutzfeldt-Jakob disease patients. Regarding genetic prion diseases, the most common mutation of prion protein gene was V180I (41.2%), followed by P102L (18.1%), E200K (17.1%) and M232R (15.3%), and this distribution was quite different from that in Europe. In particular, V180I and M232R were quite rare mutations worldwide. Patients with V180I or M232R mutations rarely had a family history of prion diseases, indicating that a genetic test for sporadic cases is necessary to distinguish these from sporadic Creutzfeldt-Jakob disease. In conclusion, our prospective 10-year surveillance revealed a frequent occurrence of dura mater graft-associated Creutzfeldt-Jakob disease, and unique phenotypes of sporadic Creutzfeldt-Jakob disease and genetic prion diseases related to the characteristic distribution of prion protein gene mutations and polymorphisms in Japan, compared with those in western countries.