The API2-MALT1 fusion gene was originally identified from a t(11;18)(q21;q21) translocation, a specific chromosomal abnormality that is found in mucosa-associated lymphoid tissue (MALT) lymphoma. Gastric MALT lymphomas positive for the API2-MALT1 fusion gene do not respond to Helicobacter pylori-eradication therapy, but otherwise, the incidence and clinicopathological behavior of colorectal MALT lymphoma with this genetic abnormality are unclear. We examined the API2-MALT1 fusion by multiplex RT-PCR method in 47 cases of MALT lymphoma and 13 cases of diffuse large B-cell lymphoma and evaluated the relevance of API2-MALT1 positivity to the clinical and pathological features. The mean ages of MALT lymphoma and diffuse large B-cell lymphoma patients were 65 (range, 37-87 y) and 58 (range, 14-85 y) years, respectively. API2-MALT1 fusion genes were detected in seven cases (15%) of MALT lymphoma and one case (8%) of diffuse large B-cell lymphoma. In MALT lymphomas, the tumor size in API2-MALT1-positive cases was 62 +/- 39 mm (mean +/- SD), statistically larger than that in API2-MALT1-negative cases (25 +/- 19 mm; P <.01). The API2-MALT1-positive cases demonstrated more advanced clinical stages and a male predominance, compared with API2-MALT1-negative cases. Thus, API2-MALT1-positive tumors should be cared for as a more aggressive subgroup and be followed for a longer time.