When node metastases are identified in the neck, but the clinical assessment using imaging and endoscopic procedures does not enable identifying the primary site, the established diagnosis is metastasis with unknown primary site. In these cases the majority of patients have the malignancy confined to the supraclavicular area, thus making it unnecessary to perform a systematic search.

The majority of metastases are squamous cell carcinoma, the most common tumor originating in the mucous membranes of the head and neck.

The lack of a primary site forces us to not only treat the neck, but also probable primary sites and the contralateral neck. However, the morbidity brought about by this treatment is currently questioning its routine use.

The great majority of patients cannot be treated with only one therapeutic treatment and must be subjected to surgery, radiotherapy, or an association of chemoradiotherapy, but the key to the therapeutic decision is correct staging.

Intensity modulated radiotherapy, and the value of the human papilloma virus and Epstein Barr virus in the etiology of head and neck cancer have changed the therapeutic approach to this entity. The purpose of this study is to offer readers the latest diagnostic-therapeutic bases for this neoplasia.