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Except for HPV-induced cancers of the oropharynx, survival rates in patients with squamous cell carcinoma of the head and neck (HNSCC) have not changed substantially over the last decades. Salvage surgery plays an important role where primary treatment was unsuccessful since 50% of advanced-stage patients relapse after nonsurgical primary treatment. Depending on a variety of factors, a considerable number of patients in whom primary treatment was not successful can still be cured by salvage surgery. It is the goal of this review to elucidate these factors with the aim to counsel patients and their relatives realistically about the chances of being cured.