The management of patients with cervical node metastasis (CNM) from carcinoma of unknown primary (CUP) often includes several radiographic studies and invasive procedures that are only successful in detecting an occult primary tumour in less than 25% of the cases. In this prospective study we have assessed the role of total body positron emission tomography (PET) using an 18-F-fluorodesoxyglucose (FDG) in the detection of primary tumours in patients with metastases from CUP. Thirteen patients with lymph node metastases from cytologically verified CUP have undergone total body FDG PET which confirmed the possibility of lymph nodal lesion; all patients have also undergone conventional imaging with CT and/or MRI. The data obtained with the FDG-PET method have subsequently been confirmed both by the histopathological examination and by the clinical course of the disease. The current work aims at assessing and defining the effectiveness of the FDG-PET method during the diagnostic work-up of laterocervical metastasis from CUP conventionally examined with CT and/or MRI; based on our results, we recommend a flow-chart for the clinical-diagnostic management of the patient affected by laterocervical metastasis in the absence of known primary.