The main goal of this study was to identify the main distinctive radiographic characteristics of different unilocular radiolucent mandibular lesions based on the criteria used by different groups of specialists during the process of radiograph interpretation to arrive at a correct diagnosis. A total of 24 panoramic radiographs were selected exhibiting the following lesions: ameloblastoma, keratocystic odontogenic tumor, dentigerous cyst and simple bone cyst. Six cases of each pathology were analyzed by 3 specialists from 4 related areas (pathologists, stomatologists, radiologists and oral surgeons). A number of important distinctive features and confounding characteristics that are liable to misinterpretation were pointed out by the specialists during the analysis. The method of generalized estimating equations (GEE) was used to estimate the probability of correct diagnosis according to the specialization of the examiner and the type of lesion and no significant relation was found (p>0.05 for all variables). The overall percentage of correct diagnosis among the specialists was around 56%, which shows that these lesions are of difficult radiographic diagnosis. Although the specialty of the examiners did not influence the results, i.e., the 4 different kinds of specialists showed the same diagnostic capacity, the criteria used for interpreting the same lesions were often different among the specialists. The compilation of these criteria enabled the identification and selection of some useful distinctive radiographic characteristics to formulate diagnostic hypothesis of unilocular radiolucent lesions. The radiographic diagnosis of the unilocular radilucent mandibular lesions is particularly difficult and the histopathological examination is essential to make the definitive diagnosis.