Aim of work: To evaluate the significance of PET/CT in detection of the primary of metastases of unknown origin and its role in changing management. Patients and methods: A prospective analysis of 123 patients, with pathologically proved or clinico-radio logically suspected metastatic lesions of unidentified primary. All patients had previous examination and investigational check-up tests including labs, radiologic studies and histopathology before undergoing 18FDG PET/CT study, with a follow-up period of 12 months. Results: This study included 66 males and 57 females with mean age 53.98±12.9 (range=23-85) years. Main sites of presenting metastases were bone (29%) and lymph nodes (22%) followed by liver (17%) and brain (11%). Histopathology revealed poorly differentiated carcinomain 42% of patients; however, 27% of patients came with no pathology. PET/CT identified the primary site in 71 patients with commonest site in 16 patients in lung followed by pancreas and breast (9 patients each). False positive was evident in 6 patients, and it excluded malignancy in 19 patients. False negative results were found in 27 studies, 24 of which remained unknown till the end of follow-up period. Sensitivity, specificity, PPV, NPV and accuracy were 72%, 76%, and 79%, 41% and 73% respectively. PET/CT identified additional sites of metastases in 64 patients. PET/CT altered the management in 90 patients by avoiding unnecessary chemotherapy in negative patients or providing treatment targeting known primary tumor, including surgery with curative intent in 9% of patients. During the follow-up period of the 71 patients, 12 patients achieved complete response, 12 patients showed partial response and 25 patients had stable disease. Conclusion: 18F-FDG PET/CT is additiveimaging modality that help in early detection of the primary malignant site in patients with MUO and so enabling selection of suitable management protocols that might improve patients' outcome.