p53 aberrations are the most common genetic alteration found in human tumours and this review summarizes the current understanding of the clinical significance of p53 abnormalities. Immunohistochemical and molecular techniques can demonstrate alterations at the protein and gene level, respectively, but with a significant discordance between the findings of either technique. The tumours evaluated in this review include cancers of the breast, lung, gastrointestinal tract, genitourinary tract, and others. In most cases, only data on p53 protein are available and in each of these tumour types discrepant conclusions on the clinical value of p53 abnormalities as prognostic indicators have been reached. The role of p53 in the context of anticancer adjuvant therapy has also been analysed. Experimental data suggest that p53 affects the apoptotic response to anticancer agents, but this has not yet been proven in a clinical series where this demonstration and its effect on therapy could represent one of the most important endpoints in p53 clinical research. The use of standardized techniques to evaluate p53 gene mutation and protein accumulation within controlled clinical series of patients entering prospective trials is essential to answer the many remaining questions on the clinical significance of p53 aberrations.