In the present study, we molecularly and clinically characterized a single-nucleotide variant (NM_000314.4:c.-1026C>A, rs34149102 A allele) located in the promoter region of the phosphatase and tensin homolog (PTEN) gene, which we identified in an Italian family with a history of gastroesophageal junction (GEJ) adenocarcinoma and breast cancer. Here, PTEN is linked to gastroesophageal junction adenocarcinoma.