Gastric MALT lymphoma shows unique features including regression by Helicobacter pylori eradication and API2-MALT1 fusion. We performed a molecular and clinicopathologic study for 115 cases. All eradication-responsive cases were devoid of API2-MALT1 fusion. All tumors positive for the fusion and all negative for H. pylori infection were nonresponsive to the eradication. Consequently, gastric MALT lymphomas were divided into three groups: Eradication-responsive and fusion-negative (group A, n = 72), eradication-nonresponsive and fusion-negative (group B, n = 22), and eradication-nonresponsive and fusion-positive (group C, n = 21). Group A tumors were characterized by low clinical stage and superficial gastric wall involvement, and group C tumors by low H. pylori infection rate, advanced clinical stage, and nuclear BCL10 expression. All group C tumors showed exclusively low-grade histology. Group B tumors, which have not been well recognized, frequently showed nodal involvement, deep gastric wall involvement, and advanced clinical stage, and sometimes an increased large cell component. A multivariate discriminant analysis revealed that responsiveness to the eradication could be predicted accurately by negative API2-MALT1 fusion, positive H. pylori infection, low clinical stage, and superficial gastric wall invasion, the former being the most important factor for the prediction. This 3-group categorization may be helpful for a comprehensive understanding of gastric MALT lymphoma.