Although differentiation between central chondroid tumors is important, their parallelism makes it a diagnostic conundrum for clinicians and radiologists. The objective of this study was to evaluate the efficiency of quantitative single photon emission computed tomography (SPECT)/computed tomography (CT) in differentiating grade I chondrosarcomas from enchondromas. We reviewed SPECT/CT images of patients with enchondromas and grade I chondrosarcomas arising in the long bones. Volume, mean standardized uptake value (SUVmean), and maximum standardized uptake value (SUVmax) of tumors were calculated from SPECT/CT images. In addition, clinical characteristics and radiological information were assessed. Of a total of 34 patients, 14 had chondrosarcomas. Chondrosarcoma group had significantly larger volume, and higher SUVmean and SUVmax of tumors than enchondroma group. There was no significant difference in age and tumor size between two groups. Areas under the receiver-operating characteristic curve (AUCs) for tumor volume, SUVmean, and SUVmax were 0.727, 0.757, and 0.875. In pairwise analyses, SUVmax had larger AUC than SUVmean (p = 0.0216). With a cutoff value of 15.6 for SUVmax, its sensitivity and specificity were 86% and 75% for differentiating between enchondroma and grade I chondrosarcoma. Quantitative SPECT/ CT is a potential method to differentiate grade I chondroarcomas from enchondromas in patients with central chondroid tumors. Differentiation between central chondroid tumors is important because surgical treatment is the only curative management for patients with grade I chondrosarcoma. A wait-and-see policy is permissible for enchondromas in consideration of long-term prognosis 1,2. Nevertheless, their parallelism makes it a diagnostic conundrum for clinicians and radiologists to distinguish them 3. Clinical symptoms such as spontaneous pain are believed to be helpful in distinction. However, patients with enchondroma uncommonly complained of resting pain and the presentation without symptom does not rule out malignancy 4. Although poorly defined margin, deep endosteal scalloping, the size over 5 cm, periosteal reaction without a history of trauma, and epiphyseal location in plain radiography favor chondrosarcoma, the discriminating power of this set of parameters is limited 2,5. While chondrosarcomas with lobulated lesion, osseous destruction and fibrovascular septae on magnetic resonance imaging (MRI), and early enhancement pattern on dynamic contrast-enhanced (DCE) MRI can be used for differential diagnosis of chondroid tumors 6 , their usefulness remains controversial 5,7,8. Interpretation of radiological findings demonstrated low reliability for grading of cartilaginous tumors, even among expert radiologists 3. Diffusionweighted MRI and quantitative assessment by apparent diffusion coefficient values are expected to be attributed to more accurate and consistent diagnosis for that reason. However, the role of diffusion-weighted MRI is also questioned 3,9. Although F-18 fluorodeoxyglucose positron em...