Although the cyclooxygenase-2 (COX-2) pathway of the arachidonic acid cascade has been suggested to play an important role in colon carcinogenesis, there is little information concerning the identity of phospholipase A2 (PLA2) involved in the arachidonic acid release in colon tumors. Here, we compared the potencies of three types of secretory PLA2s (group IB, IIA and X sPLA2s) for the arachidonic acid release from cultured human colon adenocarcinoma cells, and found that group X sPLA2 has the most powerful potency in the release of arachidonic acid leading to COX-2-dependent prostaglandin E2 (PGE2) formation. Furthermore, immunohistological analysis revealed the elevated expression of group X sPLA2 in human colon adenocarcinoma neoplastic cells in concert with augmented expression of COX-2. These findings suggest a critical role of group X sPLA2 in the PGE2 biosynthesis during colon tumorigenesis.