The accumulation of radioactive tracer is associated with specific histological changes. Awareness of these changes permits a more specific interpretation of a positive bone scan, especially when correlating the radionuclide image with the plain radiographs. Increased uptake in the flow phase of an imaging study usually corresponds to differentiated vascular spaces. In the blood pool phase, tracer accumulation is caused by neovascularity, a feature of reactive granulation tissue or neoplastic angiogenesis. In the delayed phase, tracer uptake is attributable to osteoid production. With plain radiographic correlation, the manner of osteoid deposition--remodeling, endochondral, reactive, or neoplastic--can be determined. The knowledge of these histological features may help the nuclear radiologist make the correct diagnosis.