Mutations of the p53 gene are the most common genetic changes in human malignancies; therefore their detection is of practical importance. In contrast to wild-type p53 in resting normal cells, mutant p53 proteins are easily detectable by immunocytochemical methods due to their abnormally extended half-life. Several methods of immunocytochemistry can be used to analyze the presence and localization of p53 protein in cells or tissues. The most important is immunocytochemical p53 staining of sections from paraffin embedded tissues. This method is used as a relatively reliable surrogate marker for p53 mutations and has the advantage of being easy, fast, and suitable for mass screening of large archival tissue banks. Frozen sections can also be used to detect and localize the p53 proteins. p53 can also be detected in tissue culture cells. p53 can be detected in situ through a secondary antibody coupled to a fluorescent dye or an enzymatic activity that reacts with certain chromogens.