SMAD4 is tumor suppressor gene and it encodes an intracellular mediator in the transforming growth factor β (TGF β) signal transduction pathway. Somatic mutations affecting the SMAD4 gene are rare in breast neoplasms and their role in breast tumorigenesis remains unclear. However, it has been demonstrated that SMAD4 protein expression is markedly downregulated or lost in breast ductal carcinoma when compared with that in the normal breast epithelium. Loss of SMAD4 protein expression may play a role in disease progression and overall prognosis in breast cancer patients but this need to be fully elucidated.