The p53 protein plays a central role in regulating apoptosis. The loss of functional p53 is common in many cancers. In cancer cells, the dysfunctional p53 protein often maintains a misfolded, inactive conformation due to genetic mutations or posttranslational deregulation. The misfolded p53 protein can aggregate and form amyloid-like oligomers and fibrils, which abrogate the pro-apoptotic functions of p53. Therefore, the aggregation of p53 may be a crucial factor in carcinogenesis, tumor progression, and the response of cancer cells to apoptotic signals. In this chapter, we provide details on various methods for detecting p53 aggregation in cancer cell lines and tumor samples.