The chapter discusses the prevalence and characteristics of p53 mutations in various types of human cancers. P53, a tumor suppressor gene, is frequently mutated in diverse cancers, with the mutational spectrum varying among different cancer types. Transitions are more common in colon, brain, and lymphoid malignancies, while G:C to T:A transversions are more frequent in lung and liver cancers. A:T transitions are more prevalent in esophageal carcinomas. Most transitions in colorectal carcinomas, brain tumors, leukemias, and lymphomas occur at CpG dinucleotide hotspots. G to T transversions in lung, breast, and esophageal carcinomas are dispersed among multiple codons. In liver tumors from regions with aflatoxin B1 and hepatitis B virus exposure, most mutations are at codon 249. These differences suggest that both exogenous and endogenous factors contribute to p53 mutations in human carcinogenesis. The chapter also highlights the importance of understanding the etiology of these mutations to reduce cancer incidence and improve cancer prevention strategies.The chapter discusses the prevalence and characteristics of p53 mutations in various types of human cancers. P53, a tumor suppressor gene, is frequently mutated in diverse cancers, with the mutational spectrum varying among different cancer types. Transitions are more common in colon, brain, and lymphoid malignancies, while G:C to T:A transversions are more frequent in lung and liver cancers. A:T transitions are more prevalent in esophageal carcinomas. Most transitions in colorectal carcinomas, brain tumors, leukemias, and lymphomas occur at CpG dinucleotide hotspots. G to T transversions in lung, breast, and esophageal carcinomas are dispersed among multiple codons. In liver tumors from regions with aflatoxin B1 and hepatitis B virus exposure, most mutations are at codon 249. These differences suggest that both exogenous and endogenous factors contribute to p53 mutations in human carcinogenesis. The chapter also highlights the importance of understanding the etiology of these mutations to reduce cancer incidence and improve cancer prevention strategies.