The Pleomorphic Adenoma (PA) is the most common neoplasm of salivary glands. Recurrences of APs are common and increase the probability of the malignant transformation giving rise to the Carcinoma Ex Pleomorphic Adenoma (CXPA), which, although rare, is an aggressive tumor with frequent metastasis and death related to the disease. As previously reported in the literature, the Pleomorphic Adenoma Gene 1 (PLAG1) and High Mobility Group AT-hook 2 (HMGA2) genes are associated with the onset and progression of PAs and CXPAs. HMGA2 plays a role in the architectural transcription factor, modulating the threedimensional conformation of the DNA and consequently modulating the expression of several genes. The PLAG1 gene is involved in cell proliferation through the control of various target genes. In normal tissues, its activity is high during embryonic and fetal development, but in adult life, however, its participation is low or absent. The protein expression of PLAG1 and HMGA2 in 38 cases of PA, 36 cases of Recurrent PA (RPA) and 41 cases of CXAP was analyzed.