One pathologic tumor type, squamous cell carcinoma (SCC), accounts for the majority of all head and neck (HN) cancers yet is a heterogeneous malignancy (Chegini et al., J Oral Pathol Med 00:1–5, 2019). SCC arises from the squamous lining of moist mucosal surfaces of the HN, the pharynx, larynx, and paranasal sinuses. It also arises from the skin surface, with the greatest proportion of cutaneous SCC arising in the sun-exposed head and neck (Gurudutt and Genden, J Skin Cancer 2011:502723, 2011; Ouyang, Semin Plast Surg 24:117–126, 2010). In most sites of the HN, tobacco is the most common causative agent in the development of mucosal dysplasia and neoplasia (Gandini et al., Int J Cancer 122:155–164, 2008). Alcohol is a synergistic cofactor while poor oral hygiene and genetics are also contributing risk factors to the development of SCC (Hashibe et al., Cancer Epidemiol Biomark Prev 15:696–703, 2006; Hashibe et al., J Natl Cancer Inst 99:777–789, 2007). Paralleling the declining trend of smoking over the last 30 years has been an overall decline in the incidence of HN SCC, particularly in the oral cavity, larynx, and hypopharynx. Conversely, in the oropharynx there has been a rise in lingual and palatine tonsillar SCC, particularly in patients under the age of 60 years, who may have no or a limited history of tobacco and alcohol use. This increasingly common group of SCC tumors has been shown to be positive for human papilloma virus (HPV) and most commonly the high-risk HPV 16 subtype, which is responsible for anogenital neoplasms. Currently in the USA about 70% of oropharyngeal tonsillar SCC are due to HPV (https://seer.cancer.gov/statfacts/html/oralcav.html). HPV-positive SCC is more responsive to chemoradiation than HPV-negative SCC, and patients have an overall better prognosis. Patients with HPV-positive tumors who are also smokers carry an intermediate prognosis. Nasopharyngeal carcinoma (NPC) is a distinctly different neoplasm with the most common histopathological subtypes associated with Epstein–Barr virus (EBV) infection. The least common and most aggressive form (keratinizing NPC) is related to tobacco and alcohol abuse, although rare cases have demonstrated an association with HPV infection also. While our current understanding of SCC is evolving through greater molecular interrogation of these tumors, and this has resulted in recent major changes to the American Joint Committee on Cancer (AJCC) and Union for International Cancer Control (UICC) staging systems, the radiologist’s role remains largely unchanged (Amin et al., AJCC cancer staging manual, New York, Springer, 2017; Brierley et al., TNM classification of malignant tumours, Wiley Blackwell, Hoboken, 2017). At the time of diagnosis, the radiologist has key input for tumor staging. The radiologist’s roles include evaluating the full local extent of the primary, detecting perineural tumor, and assessing regional nodal and distant spread of disease. Following treatment, both baseline and surveillance imaging requires careful evaluation to detect residual or recurrent SCC, treatment complications, and second primary neoplasms. This article will review how the radiologist provides valuable input to the staging and surveillance and the overall care of patients with HN SCC and specific strategies for approaching these often-complex cases.