Sporadic gastric cancer is considered to be the result of a progressive accumulation of genotypic changes due to an adverse environment (i.e., diet and Helicobacter pylori infection). The main molecular mechanism implicated in cancer-related molecular alterations is of epigenetic nature, which includes DNA methylation and histone modification. Diet may influence the methylation status supplying methyl groups S-adenosyl-methionine formation, modifying DNA methyltransferase activity and influencing DNA demethylation activity. H. pylori may affect DNA methyltransferase directly or through inflammatory mediators (e.g., reactive oxygen species or nitric oxide). In conclusion, gastric cancer is a multistep process due to an adverse environment over a long period of time. Dietary habit and H. pylori infection can induce epigenetic alterations that, in turn, trigger gastric carcinogenesis.