Highlights•The Lynch syndrome (LS) is an autosomal dominant condition usually characterized by germline pathogenic variants in DNA mismatch repair (MMR) genes.•We report about a 47 years-old female affected by endometrial cancer (EC) with an extremely rare germline heterozygous variant in the MSH2 gene (c.562G > T p. (Glu188Ter), exon 3) that is likely pathogenic.