ABSTRACT Background We recently reported that a direct contact of Helicobacter pylori (HP) with B cells resulted in CagA translocation into the cells (Cancer Res 2010;70:5740-8). The translocated CagA further activates extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), and up-regulates the expressions of Bcl-2 and Bcl-xL. In this study, we sought to verify if CagA exists in the malignant B cells of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Methods Expression of CagA protein, phospho-SHP-2, phospho-ERK, phospho-p38MAPK, Bcl-2 and Bcl-xL in a series of 26 gastric MALT lymphoma was determined by immunohistochemistry. Western blot analysis was done to confirm immunohistochemical detection of CagA and biopsies from non-gastric MALT lymphoma served as negative controls. The association of CagA expression and the tumor response to HP-eradication (HPE) therapy was evaluated in 77 stage IE/IIE1 low-grade gastric MALT lymphoma patients. Results The expression of CagA was detected in 35 (45.5%) of 77 patients. CagA expression was closely associated with the expression phospho-SHP-2 (P = .016), phospho-ERK (P Conclusion CagA protein can be translocated into malignant B cells of MALT lymphoma. The expression of CagA in lymphoma cells appears to be biologically and clinically significant. Disclosure All authors have declared no conflicts of interest.