For a long time, scientific medical research has been focusedto the study of oncogenesis of different neoplasms, leading to the definition ofseveral exogenous factors as well as cellular mechanismsable to promote or to prevent cancer development. Molecular mechanisms are extremely variable making itdifficult to understand their role in many different pathological processes, particularly, in tumor growth. Autophagy is a self-degradative mechanism expressed at the basal level in all cells tomaintain cellular homeostasis,by the regulation of the turnover of molecules and organelles. Several Authors suggested that the autophagic mechanisms prevent tumor development, thanks to their ability to eliminate organelles and damaged or mutated proteins, thus improving tumor-antigen presentation, but, on the other side, they could be involved in etiopathology of cancer and in the resistance to chemotherapy. Apoptosis is the best known mechanism of programmed cell death that is involved in both physiological and pathological events because it is able to maintain the homeostatic balance in response to pro- or anti-apoptotic stimuli, while dysregulation of apoptosisis implicated in many diseases, including cancer, acquired immune deficiency syndrome,neurodegenerative disorders, and viral and bacterialinfections. Several studies show that may exist a correlation between autophagy and apoptosis, and it has been demonstrated that autophagic mechanisms are also regulated by many factors related to the process of programmed cell death. Scientific literature describes different mechanisms of interaction between apoptosis and autophagy that explain their role in regulation of the cell homeostasis and the aim of this study was to understand how the balance between these different processesshould be involved in tumor promotion of domestic animals (in particular, in canine osteoblastic osteosarcoma). Our work was focusedon immunohistochemical study of p53, Bcl-2 and Ki-67, that are involved in the mechanisms of regulation of cell cycle and therefore responsible for the activation and/or inhibition of autophagy and apoptosis mechanisms. Immunohistochemical investigation have been conducted on samples of spontaneous canine osteoblastic osteosarcoma and the results obtained show that in all examinedcases there wasasignificative overexpression of Bcl-2 in the cytoplasm of tumor cells. Also p53 was overexpressed in osteoblastic cell of all investigated cases and its localization is both cytoplasmic and nuclear. Finally, Ki-67 was overexpressed in the nucleus of all samples. The results suggested that in all samples there is an important proliferation activity emphasized by the expression of Ki-67 that is an important marker of mitotic index in tumors. The expression of Bcl-2 suggested that apoptotic activity is inhibited in favor of cell survival mechanisms such as autophagy. Finally, the mostly cytoplasmicexpression of p53 suggested a tendency of tumor cells to activate the autophagic response. All results obtained allow us to hypothesize that the autophagic activity maybe closely related to tumor progression and further investigations are necessary to deepen the roles of these specific biomolecular mechanisms.