Purpose: To evaluate the utility of FDG-PET in detecting primary tumors in patients with metastatic disease from unknown primary tumors.Methods: 12 patients with metastases from unknown origin after unsuccessful conventional diagnostic procedures were studied. 5 had lymph node metastases (2 axillary, 2 cervical, 1 mediastinal), 3 multiple metastases, 1 in the lung, 1 in the cava vein, 1 in the brain and 1 in adrenal glands. Patients received 400MBq FDG intravenously, and whole body images were acquired 60 min. after injection with an ECAT EXACT HR+. PET results were compared with histological and clinical findings.Results: All but one metastatic lesion was identified by PET. Additional metastases were visualized in 4 patients. In one helped to guide biopsy for histological diagnosis. In 4/11 patients FDG-PET did not reveal lesions suspected to be primary tumor. FDG-PET identified primary tumor in 8/11 patients (breast: 2, pancreas: 2, base of tongue: 1, adrenal gland: 1, lung: 1, stomach: 1). In 4 of them (33% of total) primary tumor was confirmed either histologically or by the clinical evolution (breast: 2, lung: 1, pancreas: 1). In 1 patient FDG-PET was false positive (base of tongue). 3 patients positive FDG-PET have not yet been confirmed. FDG-PET influenced therapeutic procedures in 4 patients (33% of total). 2 underwent surgery (breast), 1 received specific chemotherapy (lung) and 1 palliative chemotherapy (pancreas).Conclusions: Our preliminary results suggest that FDG-PET is a non-invasive technique useful in the detection of unknown primary tumors, can influence in selecting appropriate therapeutic management and could guide biopsies for histologic analysis.