Objective To explore the key points of differential diagnosis between benign and malignant masses in the lateral neck so as to improve the accuracy of preoperative diagnosis via retrospectively analyzing the clinicopathological data of adult patients with initially diagnosed as benign cervical cysts.Methods A retrospective study was performed to all adult patients with initial clinical diagnosis of branchial cleft cyst or cystic hygroma in our department from Jan 2014 to Dec 2021. The analyzed data included the clinical, radiological and pathological records of all cases.Results A total of 37 patients were diagnosed as cervical benign cysts, and the overall rate of malignancy was 13.5 % (5/37), including cervical lymphatic metastasis from oropharyngeal squamous cell carcinoma in two cases and papillary thyroid carcinoma in three. The presence of septa and uneven thickening of cystic wall in the cervical mass was an independent predictor of malignant metastatic lymph nodes in solitary cystic mass of the lateral neck in adults (P=0.003, 0.005).Conclusion Solitary cystic mass of the lateral neck in adults needs to be vigilant for cervical metastatic carcinoma of unknown primary site. Multiple diagnostic methods should be combined to exclude cervical metastatic carcinoma of unknown primary site in adults with solitary cystic mass in the lateral neck, especially for those with septa and uneven thickening of cystic wall.