The so-called calcifying odontogenic cyst (COC) represents a heterogeneous group of lesions that exhibit a variety of clinico-pathologic features. It is an uncommon lesion and represents less than 2% of all odontogenic cysts and tumors. Recently, these lesions have been reclassified as calcifying cystic odontogenic tumors (CCOT), according to the new World Health Organization (WHO) classification. CCOT are frequently found in association with, or containing areas histologically identical to, various types of odontogenic tumors, such as complex/compound odontomas. This work analyzed clinical and histological data deriving from 13 patients affected by CCOT associated with odontomas. Moreover, a confocal laser scanning microscope (CLSM) analysis was undertaken to further a better understanding of the nature of this peculiar lesion.