OBJECTIVE The differentiation of the ameloblastoma and odontogenic keratocyst directly affects the formulation of surgical plans, while the results of differential diagnosis by imaging alone are not satisfactory. This paper aimed to propose an algorithm based on convolutional neural networks (CNN) structure to significantly improve the classification accuracy of these two tumors. METHODS A total of 420 digital panoramic radiographs provided by 401 patients were acquired from the Shanghai Ninth People's Hospital. Each of them was cropped to a patch as a region of interest by radiologists. Furthermore, inverse logarithm transformation and histogram equalization were employed to increase the contrast of the region of interest (ROI). To alleviate overfitting, random rotation and flip transform as data augmentation algorithms were adopted to the training dataset. We provided a CNN structure based on a transfer learning algorithm, which consists of two branches in parallel. The output of the network is a two-dimensional vector representing the predicted scores of ameloblastoma and odontogenic keratocyst, respectively. RESULTS The proposed network achieved an accuracy of 90.36% (AUC = 0.946), while sensitivity and specificity were 92.88% and 87.80%, respectively. Two other networks named VGG-19 and ResNet-50 and a network trained from scratch were also used in the experiment, which achieved accuracy of 80.72%, 78.31%, and 69.88%, respectively. CONCLUSIONS We proposed an algorithm that significantly improves the differential diagnosis accuracy of ameloblastoma and odontogenic keratocyst and has the utility to provide a reliable recommendation to the oral maxillofacial specialists before surgery.