Objective Evaluate the role of neck dissection (ND) as the sole treatment modality for patients with cervical head and neck squamous cell carcinoma of unknown primary (HNSCCUP). Design Systematic review of observational cohort studies with qualitative synthesis. Setting PubMed, Ovid EMBASE, and Cochrane Controlled register of Trials (CENTRAL) were screened from January 2000 up to October 2021. Participants HNSCCUP patients undergoing ND. Main Outcome Measures The primary outcome was 3-year overall survival (OS). Secondary outcomes included disease-free survival (DFS), primary emergence, regional recurrence, and distant metastasis. Results Fourteen eligible studies were identified, including 1,780 patients, of whom 294 received ND as their sole treatment (seven studies) with 3-year OS ranging from 43.9% to 100%. 3-year DFS was reported in four studies (n=62) ranging from 42.8% to 67.0%. 5-year OS and DFS were available in three studies (n=31), ranging from 36.6% to 75.0%, and 43.6% to 67.0%, respectively. The rate of primary emergence ranged from 11.1% to 33.3% (seven studies, n=157), regional relapse from 0.0% to 50.0% (five studies, n=60), and distant metastasis from 0.0% to 3.3% (three studies, n=45). Patients undergoing ND as a sole treatment had predominantly p16 positive N1 (TNM7) disease without ECS. Conclusion Outcomes for HNSCCUP patients undergoing ND alone range widely in the literature but appear reasonable in a subset of patients with early stage p16 positive disease. Data is lacking for p16 negative disease where the potential primary site is more varied and primary emergence appears more common.