It is estimated that up to 300 of the human body’s circa 800 lymph nodes reside in the head and neck (Fig. 22.1) (Iwanaga et al. 2021). Although most lymphadenopathies result from benign viral-reactive etiologies, insidious pathologies of the head and neck often involve the lymphatic system. For instance, the mere presence of intranodal metastasis dramatically affects head and neck cancer staging (Agarwal et al. 2018; Lin et al. 2006; Saindane 2013). Scientific understanding of the lymphatic system of the head and neck progressed from the foundation laid by French anatomist-physician Rouviere. Dr. George Crile described radical neck dissection, which, though it was effective for his patients, has undergone major improvements during the last 100 years (Subramanian et al. 2006). Today, advanced imaging and sentinel node biopsy (SNB) guide medical decision-making, and improvements in the surgical procedure of neck dissection have led to improved outcomes. Advances in nuclear medicine imaging allow us to anticipate yet greater accuracy in staging head and neck cancers (de Bree et al. 2015; Vidal-Sicart and Valdés Olmos 2021).