Background: It is difficult to differentiate giant cell tumors of the bone (GCTB) from chondroblastoma around the knee based on imaging findings. This study analyzed the imaging features of these 2 diseases for better differentiation.Methods: This retrospective cross-sectional cohort study reviewed data of patients with pathologically confirmed GCTB (n=81; age 15-75 years; median age 33 years) and chondroblastoma (n=18; age 12-34 years; median age 14 years). In all, 18 imaging signs were analyzed.Results: Patients with chondroblastoma were relatively younger than those with GCTB. On imaging, lesion length was significantly (P<0.00001) smaller in chondroblastoma {range 15.80-78.30 mm; mean [± standard deviation (SD)] 34.15±18.24 mm; 95% confidence interval (CI): 24.05-44.25 mm} than in GCTB [range, 30.10-117.50 mm; mean (±SD) 59.73±15.28 mm; 95% CI: 56.24-63.22 mm]. Significantly more (P<0.05) chondroblastoma lesions had calcification (76.5% vs. 1.3%), lobulation (77.8% vs. 32.1%), and swelling range >15 mm (84.6% vs. 41.1%) than did GCTB lesions, whereas significantly more (P<0.05) GCTB lesions were greater than half the host bone diameter (74.1% vs. 16.7%) and had a lesion long axis that was consistent with that of the host bone (98.8% vs. 27.8%). There were no significant differences (P>0.05) between the 2 tumors in the remaining 11 imaging signs.Conclusions: A narrow zone of transition, intratumor calcification, lobulation, tumor transverse diameter greater than the bone diameter, maximum lesion length, consistency between the tumor and bone long axes, and edema range around the lesion >15 mm are parameters that can be used to differentiate GCTB from chondroblastoma around the knee.