Previous findings indicate epigenetic silencing of SOCS3 as a major mechanism for the loss of function of SOCS3 [7], but the fact that cell lines and some HNSCC cases still present SOCS3 expression and have similar invasive biological behavior is intriguing and suggest an alternative mechanism for the impaired function of SOCS3, if this gene is relevant for tumor progression. The gene discussed is SOCS3; the disease is head and neck squamous cell carcinoma.