Central nervous systems (CNS) malignancies, as others cancers, are formed by the uncontrolled cell growth that involves the sequential accumulation of alterations in genes controlling cell proliferation, lifespan, responses to stress, relationships with neighbors, and gene homeostasis. These genetic alterations can be achieved by intragenic mutations, chromosome alterations or epigenetics modifications, all playing important role in the activation or inactivation of key genes, such as oncogenes and tumor suppressor genes. Some of these mutations can be most frequently encountered in specific cancers or group of cancers and correlated with tumor biologic behavior and have implications on diagnosis, prognosis or treatment. Biomarkers are important oncology tools in diagnostic, monitoring disease progression, helping in determining prognosis and predicting therapeutic response. Biomarkers vary from specific proteins and antigens to unique genetic, epigenetic or cytogenetic profiles, but common to all markers is that they provide specific information to a disease process. They function as supplementary and rarely supplanting, the histopathologic examination of tissues that is still the mainstay of traditional oncologic pathology. For this reason, we intend to compile the vast information about the important contribution of TP53 gene as a biomarker in CNS cancer genesis, progression, stratification, prognosis, treatment and its importance to future targeted therapies.