Since data on B7-H3 and B7-H4 expression patterns in HNSCC are still limited, mostly relate to small patient cohorts, and have not been studied together, we investigated the impact of both markers on patient survival in a retrospective single center patient cohort in a tissue microarray (TMA) format and the TCGA dataset. This evidence concerns the gene VTCN1 and head and neck squamous cell carcinoma.