Aims: Involvement of caspase (C)-3 has been implicated in β-cells from diabetic subjects. This study is aimed to immunocytochemically identify cleaved caspase-3 (CC-3) positive cells in pancreatic endocrine tumors (PETs) compared with control islets. Methods: Using commercially available rabbit anti-CC-3, immunocytochemical staining was performed in 42 cases of PETs compared with control islets. Results: Control islets revealed some CC-3 positive cells, ranging 3.6 to 7.3 % of total islet cells. Small islets in the pseudocapsule of PETs showed higher immunopositive cells at about 9 % for CC-3, suggesting an accelerated apoptosis in these compressed, elongated islets before proceeding to imminent cell death. Majority of primary PETs except 9 cases were negative for CC-3 immunostaining: five insulinomas, one somatostatinoma, one gastrinoma and one pancreatic peptidoma (PPoma) were positive for CC-3. Conclusions./Interpretation: Majority of primary PETs (28/37, 76 %) were negative for CC-3, suggesting that majority of PETs are not on apoptotic program of the normal islets. Since 21 of 24 (88 %) of potentially malignant primary non-ß cell PETs were negative, whereas 5 of 12 (42 %) benign insulinomas were positive for CC-3 immunostaining, CC-3 negative immunostaining may serve as a possible malignant marker for all PETs.