BACKGROUND: To distinguish between low-grade lymphoma and reactive lymphoid infiltrate can be demanding for pathologists. Demonstration of B-cell monoclonality by polymerase chain reaction (PCR) analysis of immunoglobulin heavy chain is useful as referential data. Telomerase activity, which is frequently detected in malignant tumors while being undetectable in normal tissues, may also have a supportive role in the diagnostic procedure, but has not been investigated in specimens of primary gastric lymphoma. METHODS: Telomerase activity was qualitatively and quantitatively evaluated, using fluorescence-based telomeric amplification assay protocol (TRAP) analysis, in 16 malignant lymphoma and related specimens, including 7 specimens of low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, among which specimens before and after Helicobacter pylori eradication were evaluated from five patients. RESULTS: Telomerase activity was detected more frequently (6 of 7 specimens) at higher levels in high-grade lymphoma compared with low-grade MALT lymphoma. It was detected in 3 of 7 specimens of low-grade MALT lymphoma, but was undetectable either at the stage of Helicobacter pylori-induced gastritis or after H. pylori eradication therapy. CONCLUSION: Telomerase activity evaluated by fluorescence-based TRAP analysis was detectable late in the process of evolution of MALT lymphoma and was undetectable early in the process of regression. It was frequently and overtly elevated in high-grade lymphoma. Telomerase activity may have a role in confirming the histologic diagnosis of primary gastric lymphoma.