SMAD4 is a tumor suppressor gene encoding an intracellular mediator in the transforming growth factor β (TGF β) signal transduction pathway. SMAD4 mutations have been observed in ~3% of cervical cancers. Functional inactivation of SMAD4 was found in 4 of 13 cervical squamous cancer cell lines, mostly due to homozygous loss. Loss of protein expression did not correlate with loss of heterozygosity and mutations in cervical squamous carcinomas; however, it was associated with poor disease-free and overall 5-year survival in one study. The predictive and prognostic significance of SMAD4 mutations in cervical cancers needs further elucidation. Results should be interpreted in conjunction with other laboratory and clinical findings.