Background: This research seeks to assess the immunohistochemical (IHC) expression of Mothers against decapentaplegic homolog 4 (SMAD4) in pancreatic ductal adenocarcinoma (PDAC), explore its association with Human Epidermal Growth Factor Receptor 2 (HER2) expression, and to assess its relation to different PDAC prognostic clinico-pathological variables. The association of SMAD4 and HER2 IHC expression with patients' disease-free survival (DFS) and overall survival (OS) is also evaluated. Methods: This retrospective cohort research had 83 patients who were diagnosed with primary PDAC from surgical resection specimens at the