Abstract: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 paraffinembedded 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.