Still, our findings may serve as hypothesis-generating data and, if validated in larger prospective series, may justify more aggressive neck management at presentation and treatment of HNSCC patients exhibiting high VEGF-C mRNA expression with targeted therapies (anti-VEGF-C antibodies, VEGFR3 tyrosine kinase inhibitors), either upfront or at recurrence, in order to optimise their outcome. This evidence concerns the gene VEGFC and head and neck squamous cell carcinoma.