PURPOSE: To evaluate the diagnostic ability in differentiating between ameloblastoma and odontogenic keratocyst according to the imaging modalities and observers. MATERIALS AND METHODS: We evaluated thirty-six cases of ameloblastomas and forty-seven cases of odontogenic keratocysts all histologically confirmed. Six oral and maxillofacial radiologists diagnosed the lesions by 3 methods: using panoramic radiograph, using computed tomograph (CT), and using panoramic radiograph and CT. The observers were classified by 3 groups: group 1 had experienced over 10 years in oral and maxillofacial radiologic field, group 2 had experienced for 3-4 years, and group 3 was in the process of residentship. After over 2 weeks, the observers diagnosed them by the same methods. RESULTS: The ROC curve areas except for group 3 were the highest with interpretation using panoramic radiograph and CT, followed by interpretation using CT only, and the lowest with interpretation using panoramic radiograph only. The overall difference was not found in diagnostic ability among groups in using panoramic radiograph only, but there was difference in diagnostic ability of group 1 and 2 vs 3 in using CT only, and combination panoramic radiograph and CT. CONCLUSIONS: To differentiate between ameloblastoma and odontogenic keratocyst more accurately, the experienced oral and maxillofacial radiologist should diagnose with combination of panoramic radiograph and CT.