Background/Aims: Tyrosine phosphorylation of the EPIYA motif in Helicobacter pylori CagA (CagA-P) plays an important role in toxic reaction. Diffuse-type gastric cancer (DGC) has a poor prognosis. We tried to clarify the expression level of CagA-P in DGC patients. Methods: We enrolled 42 early-stage DGC patients (DGC group; 20 males, 22 females, mean age 58.2 years) and 42 age- and gender-matched atrophic gastritis (AG) patients (AG group) as controls. We evaluated histological and serological gastritis and examined two markers; the serum titer of anti-CagA-P antibody and CagA-P expression in gastric mucosa. Results: In the DGC group, we found significantly higher corpus histological gastritis scores for activity, atrophy, and intestinal metaplasia. The titer of anti-CagA-P antibody and CagA-P expression in the corpus were significantly higher in the DGC group, especially in females (p < 0.05). Sixteen patients (38.1%) in the DGC group showed both positive markers, and the odds ratio for DGC occurrence was 4.00 (95% CI = 1.07–14.91), while that for females was 9.00 (95% CI = 1.29–62.97). Conclusions: CagA-P plays a role in active corpus gastritis, which may link to DGC carcinogenesis. Clinical quantification of CagA-P-related markers may be useful for the evaluation of DGC risk, especially in females.