Fifteen cases of high grade primary gastric non-Hodgkin's lymphomas were studied using comparative genomic hybridization (CGH) and/or fluorescence in situ hybridization (FISH) techniques. A total of 10 cases of diffuse large cell lymphoma (DLCL) with no histologically identifiable or previous history of low grade mucosa-associated lymphoid tissue (MALT) lymphoma components were examined, four by CGH and validated by FISH, and the remaining six by FISH alone. All 10 tumors showed gains in chromosome 12. Other recurring CGH findings in DLCL included copy number gains of 1q and deletions of 6q. Five cases of high grade tumors with low grade MALT components (HGM) were also examined, three by CGH and validated by FISH and two by FISH only. Only one in five HGM showed gains of chromosome 12. Other recurring CGH findings in HGM included +7q and +11q. We conclude that high grade gastric lymphomas of DLCL type were associated with gains in chromosome 12. The change was much less frequent (P < 0.01) in the HGM type, which had a percentage similar to that observed in previously reported cytogenetics/FISH studies on low grade MALT lymphomas. Our findings suggested that many DLCL were not derived from transformation of low grade MALT lymphomas.