Due to particular social and economical development, and to the impact of globalization of lifestyles, Latin America shows a superposition of cancers that are frequent in low resource countries (gastric, oesophageal squamous cell and cervical cancers) and high resource countries (cancers of breast, colon and rectum, lung and prostate). Latin America thus offers opportunities for investigating the impact on changing lifestyle patterns on the occurrence of cancer. At the molecular level, mutations in the tumor suppressor gene TP53 are common in many cancers and their distribution can be informative of the nature of the mutagenic mechanisms, thus giving clues to cancer etiology and molecular pathogenesis. However most of the data available are derived from studies in industrialized countries. In this review, we discuss current trends on cancer occurrence in Latin American countries, and we review the literature available on TP53 mutations and polymorphisms in patients from Latin America. Overall, a total of 285 mutations have been described in 1213 patients in 20 publications, representing 1.5% of the total number of mutations reported world-wide. Except for hematological cancers, TP53 mutation frequencies are similar to those reported in other regions of the world. The only tumor site presenting significant differences in mutation pattern as compared to other parts of the world is colon and rectum. However, this difference is based on a single study with 35 patients. Recently, a characteristic TP53 mutation at codon 337 (R337H) has been identified in the germline of children with adrenocortical carcinoma in Southern Brazil. Further and better focused analyses of TP53 mutation patterns in the context of epidemiological studies, should help to improve our understanding of cancer etiology in order to develop appropriate health policies and public health programs in Latin America.