99mTc-MDP bone scan has been the standard method for nuclear imaging of the skeletal system for decades, providing information about the presence, location, extent, and response to therapy in patients with bone metastasis. However, there are few improvements in radiopharmaceutical and gamma camera technology for 99mTc-MDP bone scan during the past decades, and the supply of 99mTc-MDP has become unstable because of the decrease in the number of active nuclear reactors in recent years. 18FFDG PET/CT has a proven role in staging and monitoring different cancers. However, much still remains unknown about the validity of 18F-FDG PET/CT for the detection of malignant bone involvement. The aim of this study was to review the related literatures and compare the diagnostic efficacy of 99mTc-MDP bone scan and 18F-FDG PET/CT in ruling out bone metastases. The respective advantages of the two techniques in detecting bone metastases from tumors of different positions and different types were summarized.