The majority of head and neck cancers originate from the squamous cells that line the mucosal surface of the head and neck (oral cavity, pharynx, larynx). The strongest risk factors for head and neck cancer are alcohol and tobacco use, although the incidence of human papilloma virus-associated oropharyngeal cancer is notably increasing. Infection with Epstein-Barr virus is also a risk factor for the development of nasopharyngeal and salivary gland cancers. Due to the diverse anatomic structures that comprise the head and neck, the presenting symptoms, staging, prognosis and treatment vary greatly depending on the site of origin of the malignancy. Management, accordingly, requires a multidisciplinary approach that may include surgery, radiation, and/or systemic therapy with cytotoxic chemotherapy, targeted therapy, or immunotherapy. This chapter discusses the presenting symptoms, staging, prognosis and treatment of oropharynx cancer, nasopharyngeal cancer, metastatic adenoid cystic carcinoma, and metastatic squamous cell carcinoma.