Purpose: We investigated the clinical role of F-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography(PET-CT) in the identification of the primary site and the selection of the optimal biopsy site in patients with suspectedbone metastasis of unknown primary site. Methods: The patients with suspected bone metastasis who underwent PET-CT for evaluation of primary site were enrolled inthis study. The primary sites were identified by the histopathologic or imaging studies and were classified according to the FDGuptake positivity of the primary site. To evaluate the guiding capability of PET-CT in biopsy site selection, we statisticallyanalyzed whether the biopsy site could be affected according to the presence of extra-skeletal FDG uptake. Results: Among 74 enrolled patients, 51 patients had a metastatic bone disease. The primary site was identified in 48 of 51patients (94.1%). Forty-six patients were eligible to test the association of clinical choice of biopsy site with PET positivity ofextra-skeletal lesion. The extra-skeletal biopsies were done in 42 out of 43 patients with positive extra-skeletal uptake lesions.Bone biopsies were inevitably performed in the other three patients without extra-skeletal uptake lesions. The association cameout to be significant (Fisher’s exact test, P< 0.001). Conclusion F-18 FDG PET-CT significantly contributed not only to identify the primary site but also to suggest optimal biopsysites in patients with suspected bone metastasis.