It is commonly accepted that scrapie-resistance and -susceptibility in sheep are genetically controlled. Consequently, the selection of sheep with scrapie-resistant genotypes is currently one of the most important objectives of the sheep breeding associations. However, during the last two years, new data have become available on transmissible spongiform encephalopathy (TSE) cases in TSE-resistant sheep in several European Union member states. The present paper describes the first Belgian natural "atypical" TSE case in a sheep with a scrapie-resistant genotype (ARR/ARR) detected via active surveillance. No other infections or diseases were detected in the source flock. The continued finding of new "atypical" TSE cases in sheep with scrapie-resistant genotypes undermines the purpose and efficacy of the breeding programs.