Background: Neoplasms in the head and neck region possess higher glycolytic activity than normal tissue, showing increased glucose metabolism. F-18-Flourodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) can identify an unknown primary tumor (CUP). Aim: The aim of this study was to assess the real-life performance of F-18-FDG-PET/CT in detecting primary sites in patients with cervical lymph node metastasis of CUP. Methods: A retrospective data analysis of 31 patients who received FDG-PET/CT between June 2009 and March 2015 in a CUP context with histologically confirmed cervical lymph node metastasis was included. Results: In 48% of the patients (15/31), PET/CT showed suspicious tracer accumulation. In 52% of the patients (16/31), there was no suspicious radiotracer uptake, which was confirmed by the lack of identification of any primary tumor in 10 cases until the end of follow-up. FDG-PET/CT had a sensitivity of 67%, specificity of 91%, PPV of 92%, and NPV of 63% in detecting the primary tumor. Additionally, PET/CT showed suspicious tracer accumulation according to further metastasis in 32% of the patients (10/31). Conclusion: FDG-PET/CT imaging is a useful technique for primary tumor detection in patients in a cervical CUP context. Furthermore, it provides information on the ulterior metastasis of the disease.