Intestinal metaplasia in the stomach increases the risk of gastric cancer, and the increased risk is proportional to the extent of the metaplasia. This risk could be generated by one or more mechanisms: (1) the metaplastic tissue is an early step in a multistep induction process; (2) the metaplastic tissue is an epigenetic change that raises the pH of gastric juice by replacing oxyntic mucosa, favoring the growth of a bacteria capable of generating endogenous mutagens; and/or (3) the metaplasia is only a marker for chronic gastritis due to H. pylori infection or pernicious anemia. With the last mechanism, the inflammatory response favors intramural mutagenesis that might result in metaplasia or neoplasia as independent events. Finding gene rearrangements common to both metaplastic and neoplastic tissue may establish a direct link between them, but too few have been identified to account for the large number of stomach cancers that develop in high risk populations. Histochemical and immunochemical stains that identify enzymes or mucosubstances may suggest that metaplastic epithelial cells resemble small or large intestinal cells, but they are distinctly different from both. Moreover, these stains do not indicate whether a given cytologic change is genetic or epigenetic; therefore, they cannot be used to define the relationship between metaplasia and neoplasia. It is unnecessary for practicing physicians to await resolution of this question. It can be assumed that any person with extensive metaplasia is at high risk for gastric cancer and should be subject to periodic screening. The extent of the metaplastic process is probably more important than the metaplastic subtype.