This case report describes the clinical presentation and management of a 74-year-old female with a history of rectal adenocarcinoma and ovarian cancer, who has a documented frameshift pathogenic variant in the exon 8 of <i>MSH6</i> gene and an intronic variant in the <i>BRCA2</i> gene (classified as a variant of uncertain significance), affected by NSCLC with brain metastases. This evidence concerns the gene MSH6 and non-small cell lung carcinoma.