A 66-year-old man was admitted to our hospital because of an intra-abdominal tumor and pleural effusion (PE). Immunoelectrophoresis of the serum showed immunoglobulin M (IgM) kappa paraprotein (7330 mg/dL). Abnormal plasmacytoid cells were seen in both the peripheral blood (PB) and the bone marrow (BM). Computed tomography scans showed extensive thickening of the gastric wall and bilateral massive PE without lymph node or pulmonary involvement. A histologic examination of the gastric mucosa showed a diffuse infiltration of small- to medium-sized lymphoid CD20-bearing cells, some of which showed a plasmacytoid morphology. Lymphoepithelial lesions were demonstrated with an immunohistochemical stain. The diagnosis was gastric mucosa-associated lymphoid tissue (MALT) lymphoma infiltrating to the PE, PB, and BM. The PE contained numerous lymphoid cells with plasmacytoid morphology that Southern blotting analysis showed to have a monoclonal IgH gene rearrangement pattern. The cells seemed to be divided into two populations according to their surface markers: mature B-cells (CD19+CD20+CD22+CD21+CD38-) and secretory B-cells (CD19+CD20(dim)CD22-CD21-CD38+). The reverse transcriptase-polymerase chain reaction technique detected the API-2/MLT transcript in the PE and PB. The patient had a good response to fludarabine treatment, which was followed with rituximab therapy. In general, gastric MALT lymphoma cells have a tendency to differentiate into plasma cells. In this article, we show that the cell character of API-2/MLT-positive MALT lymphoma is preserved even when the cells are disseminated. This is the first published case, to our knowledge, in which two differentiation stages of MALT lymphoma cells infiltrating into PE have been confirmed by flow cytometric analysis.