BACKGROUND: To analyze B-cell monoclonality, we need fresh materials for the Southern blotting method. In situ hybridization (ISH) for the detection of immunoglobulin light-chain mRNA can be used in formalin-fixed and paraffin-embedded tissues. However, it is difficult to detect low levels of mRNA copies. So we must develop new highly sensitive in situ hybridization methods to diagnose gastric malignant lymphoma.METHODS: We analyzed materials from 15 patients with gastric malignant lymphoma, using a new highly sensitive ISH method, and compared the results with those of a conventional method.RESULTS: With this new method, 13 of 15 cases were shown to have monotypic cytoplasmic signals, and monoclonality was detected in 3 of 4 cases of mucosa-associated lymphoid tissue (MALT) lymphoma.CONCLUSIONS: The accuracy of endoscopic biopsies is not satisfactory. However, the detection of immunoglobulin light chain mRNA, using the new highly sensitive ISH method with a non-radioactive isotope oligonucleotide probe, can be used to diagnose gastric malignant lymphoma even when conventional immunoglobulin light-chain mRNA or proteins alone cannot demonstrate the clonality.