Cyclooxygenase (COX)‐2 is a possible molecular target for suppression of colon carcinogenesis by non‐steroidal anti‐inflammatory drugs (NSAIDs). However, the expression of COX‐2 in human colonic tumors during the adenoma‐carcinoma sequence has not been elucidated. In the present study, we examined immuno‐histochemically the expression and localization of the COX‐2 protein in human colonic adenomas and cancers. Twelve human colonic adenomas and 9 advanced cancers were studied. Immunoreactive COX‐2 was predominantly and strongly expressed in sub‐epithelial interstitial cells broadly present in the surface area of adenomas. The staining pattern of macrophages was similar to that observed for COX‐2 in adenomas. Adjacent normal colonic mucosa was negative for COX‐2 expression. In contrast, COX‐2 was relatively weakly expressed in both tumor cells and interstitial cells in advanced colon cancers. In conclusion, the target of NSAIDs in preventing colon carcinogenesis may be the COX‐2 expressed in interstitial cells, possibly macrophages, of colonic adenomas. Int. J. Cancer 83:470–475, 1999. © 1999 Wiley‐Liss, Inc.