A 17-year-old girl with hereditary multiple exostoses, who was thought to have malignant transformation of an exostotic lesion, was examined by bone and Tl-201 chloride scintigraphy. Scintigraphy showed markedly intense uptake by the lesion, whereas Tl-201 imaging did not. Bone scintigraphy revealed intense to moderate uptake in other exostotic lesions, but none was apparent on the Tl-201 study. The lesion was resected and the histopathologic diagnosis was osteochondroma. Negative findings of Tl-201 scintigraphy may not exclude the possibility of chondrosarcoma, and the utility of this method may be limited. However, Tl-201 scintigraphy appears to have a useful role in differentiating malignant transformation from benign osteochondroma in hereditary multiple exostoses.