Molecular profiling confirmed MSI-H status, high tumor mutational burden (TMB-H), MLH1 promoter hypermethylation and somatic mutations in MSH2 and MSH6 genes, but without pathogenic germline variants.<h4>Conclusion</h4>We represent a molecularly validated case of dMMR duodenal adenocarcinoma, suggesting a somatic molecular pathogenesis distinct from classic intestinal cancer. Here, MLH1 is linked to intestinal cancer.