During the past few decades, researchers have been looking for parameters with an impact on the prognosis of patients with astrocytic tumors. p53 is one of the most widely investigated molecules in human gliomas. We aimed to comprehensively review the evidence for the prognostic usefulness of p53 immunohistochemical expression in paraffin-embedded tissue specimens from diffusely infiltrating astrocytomas. We conducted a systematic review of the PubMed database through December 2007 to identify cohort studies that evaluated p53 immunohistochemical expression as a prognostic marker for human astrocytomas. Estimates of significance were extracted from association tests and hazard ratios with 95% CI from actuarial curves and Cox regression analyses. A meta-analysis was performed on the studies that applied Cox models and had adjusted the hazard ratio of p53 expression with tumor grade and patients' age. We reviewed 44 publications (including 3,627 patients), 14 of which included the estimates (HR and 95% CI) derived from Cox regression. Descriptive analysis showed that most of the published articles did not contain information on important variables such as sex and age (missing from 25% and 11% of studies, respectively), previous treatment, tissue-retrieval and follow-up period (56%). The quantitative synthesis showed that p53 expression is not a significant prognostic factor (combined HR = 1.034, P = 0.531). There was no significant between-study heterogeneity and publication bias. A second meta-analysis performed only on glioblastomas showed that the overall risk of mortality in these tumors was -0.123 (-0.346 to 0.100) and was not statistically significant. After almost 20 years of research, published evidence does not substantiate the usefulness of p53 immunohistochemical expression as a prognostic marker in patients with astrocytic neoplasms.