It is difficult to identify disease entities underlying lymphadenopathy in the head and neck region based solely on imaging. This often results in metastatic squamous cell carcinoma (Sqcc)-induced lymphadenopathy being mistaken for lymphoma. This study aimed to analyze clinical characteristics and computed tomographic features that aid in distinguishing between metastatic Sqcc and lymphoma when lymphadenopathy resembles a large solitary lymphoma. The authors retrospectively enrolled 5 patients, managed between 2010 and 2024, with metastatic Sqcc mistaken for lymphoma and 9 patients with lymphadenopathy of 2cm or larger due to lymphoma. Among the 5 patients, 3 exhibited a homogeneous lymphadenopathy phenotype, whereas the remaining 2 displayed heterogeneous enhancement with multiple small necrotic areas within the affected masses. Measurement of the Hounsfield units (HU) for lymphadenopathy, the sternocleidomastoid muscle, and the submandibular gland (SMG) was conducted for each patient. The ratio of lymphadenopathy HU to the average HU of the sternocleidomastoid muscle and the SMG was significantly higher in patients diagnosed with metastatic Sqcc compared with those with lymphoma (P = 0.01). In computed tomography scans, heterogeneous lymphadenopathy or enhancement levels that approach or exceed those of the SMG may indicate the likelihood of Sqcc rather than lymphoma.