Current nuclear imaging of the skeletal system is achieved using technetium-99m (Tc-99m) methylene diphosphonate (MDP), F-18 sodium fluoride (NaF), or F-18 fluorodeoxyglucose (FDG). However, comparisons of these are rare in the literature. We present a case of a 51-year-old female with suspicious lung cancer due to main symptoms of dyspnea, nonproductive cough, and pleural pain. Tc-99m MDP whole-body bone scan (WBBS) showed multiple bony metastases. Five days later, positron emission tomography/computed tomography (PET/CT) images using both F-18 NaF and a cocktail of F-18 NaF and F-18 FDG were obtained on the same day 2 hours apart. The former showed more foci and precisely showed bony lesions compared to those obtained using Tc-99m MDP WBBS. However, the latter demonstrated more extensive radiotracer uptake, especially in osteolytic lesions, and additional soft tissue lesions in the left axillary and surpraclavicular nodes as well as the left pleura. Surgical biopsy was performed in left axillary nodes, and the metastatic carcinoma was found to be of breast origin. This case demonstrated that a cocktail of F-18 NaF and F-18 FDG could be useful in PET/CT for not only detecting more skeletal lesions but also guiding biopsies accurately to the affected tissue.