Although there is a limited role initially for staging the disease of primary bone and soft tissue tumors and for differentiation of benign from malignant lesions, nuclear medicine studies are recommended before starting treatment. A total body bone scan that includes a three phase study for the involved region helps to outline the vascularity of the lesion and both soft tissue and bony involvement, as well as involvement of other bones. A thallium 201 chloride or technitium 99m methoxy isobutyl isonitrile (SestaMIBI) tumor imaging study is recommended for baseline study and for future reference to evaluate the response to preoperative chemotherapy. This is of special importance to determine whether the patient needs an amputation or a limb-salvaging procedure. A follow-up thallium or 99mTc sesta MIBI study is not recommended early after surgery. A waiting period of at least 2 months is essential to avoid false-positive uptake caused by postoperative changes although this could be differentiated by comparing the ratios of lesion uptake in both early and delayed thallium imaging and with the ratios from the blood pool phase of the bone scan. Persistent thallium uptake in delayed images accompanied by ratios that are higher than the blood pool ratios is highly indicative of early recurrence. In the future, F-18 FDG tumor imaging acquired either on dedicated positron-emission tomography (PET) systems or by using a dual head gamma camera for coincidence detection will replace thallium and 99mTc sesta MIBI in those centers that have access to this technology. This is especially important at sites where thallium and MIBI have limitations because of normal uptake in adjacent organs.