Objective: P53 is a tumor suppressor protein described as the "guardian of the genome". In a normal cell, p53 is inactivated by its negative regulator, Mdm2. Once activated, p53 induces cell cycle arrest and apoptosis by activating various cell cycle related genes, like WAF1/ CIP1 encoding for p21. Although mutations that deactivate p53 are the most common genetic alteration found in cancer, they are rare in the context of Hodgkin's lymphoma (HL). Method: P53 immunohistochemical expression was investigated in a subset of 81 cases of primary HL. The study of the p53-downstream protein p21 was used as an indirect way of analyzing its functional status. P53 expression was correlated with proliferation, apoptosis, clinicopathological data and prognosis of the patients. Results: P53 showed a median value of 32.4 %, suggesting an upregulation of the p53 gene in HL, and a significant correlation with p21 (p=0.043) and the proliferation marker MIB1 expression (p=0.038).