An unknown primary tumor (UPT) is defined as a biopsy-proven malignancy whose anatomic origin remains unidentified after diagnostic evaluation. The estimated incidence of unknown primary tumors is 2 %-7 % of all malignancies. In 15-25 % of cases, the primary site cannot be identified even on postmortem examination. The management of these patients remains a clinical challenge. The aim of this study was to determine the role of 18FDG-PET CT in evaluation of primary tumor and its influence on therapeutic management. Fifty patients with histologically-proven metastases of UPT were included. For all patients, the conventional diagnostic work-up was unsuccessful in localizing the primary site. Whole-body PET/CT images were obtained approximately 60 min after intravenous injection of 350-425 MBq of (18) F-FDG. PET/(CT) depicted histologically verified primary tumors in 21of 46 patients (P>.05), achieving detection rates of approx. 61 % in patients presenting with cervical lymph node metastases from unknown primary tumors, and 40 % in those with extra cervical disease presentation. A positive predictive value of 72 % to 92 % was seen for all patients, depending on category of clinical presentation. In this study, PET/CT detection of additional metastases in 14.2 % (3 cases out of 21 true positives) influenced change in management plan. Considering recent studies and the results of this study, whole body FDG-PET/CT has to be considered a useful tool in evaluating metastases from an UPT, allowing an identification of primary tumors in 42 %, and modifying the stage of the disease and oncological treatment in about 50 % of cases. These results suggest the use of PET/CT with FDG in an early phase of the diagnostic evaluation to optimize the management of these patients.