Introduction : We studied the relation between premalignant gastric lesions and cyclooxygenase-2 (COX-2) expression. Methods : The study included 254 patients, who were histologically diagnosed with chronic active gastritis, atrophy, dysplasia and metaplasia. Gastric biopsy specimens of the patients were histopathologically examined in terms of the presence of Helicobacter pylori (H. pylori) infection, atrophy The Operative Link for Gastritis Assessment; (OLGA staging system), dysplasia (Vienna classification), and metaplasia (Sydney classification). COX-2 expression was investigated by immunohistochemical staining. COX-2 immunoreactivity score was calculated as the product of staining intensity and staining area. A score of >1 was defined as COX-2-positive expression. Results : Of these patients, 84 (33.1%) had negative COX-2 expression (Score 0 and Score 1) and 170 (66.9%) had positive COX-2 expression (Score 2 and Score 3). We found that in patients with a moderate-marked metaplasia, or with moderate-severe atrophy, a higher OLGA stage, or with dysplasia, the COX-2 expression was found to be higher than those with mild lesions. In 59.8% of the patients H. pylori was positive. While, the rate of severe atrophy was higher in H. pylori-positive patients; no significant difference was determined between the H. pylori-positive and H. pylori-negative patients regarding age, smoking status, intestinal metaplasia grade, dysplasia, and COX-2 expression. Conclusion : We found a relation between the level of COX-2 expression and the grade of premalignant gastric lesions. COX-2 plays an important role in the gradual process resulting eventually in gastric cancer.