While typically characterized by loss of specific MMR protein pairs, the concomitant loss of all four MMR proteins (MLH1, PMS2, MSH2, MSH6) is scarcely documented, with molecularly confirmed cases being exceptionally rare.<h4>Case presentation</h4>We presented a case of duodenal adenocarcinoma whose contrast-enhanced 64-row CT and PET/CT demonstrated characteristic features highly suspicious for malignancy. The gene discussed is MLH1; the disease is duodenal adenocarcinoma.