The B-cell lymphomas of the gastrointestinal (GI) tract have represented a field of extensive research ever since a close association was shown with such chronic inflammatory processes as Helicobacter pylori infection. Evidence suggested that the mucosa-associated lymphoid tissue induced by inflammation and autoimmune processes is the environment that gives rise to the small-cell lymphomas of the GI tract (eg, extranodal marginal zone B-cell lymphoma according to Revised European-American Classification of Lymphoid Neoplasms and the World Health Organization Classification of Neoplastic Diseases of the Hematopoietic and Lymphoid Tissue). The small B-cell lymphoma may then progress to highly malignant variants. The B-cell lymphomas of the GI tract may present a stepwise model for lymphomagenesis and progression. This review covers molecular biology and molecular cytogenetic aspects that lead to new insights into the biology of GI lymphomas and potential prognostic factors.