This study was designed to determine the expression of p16, p53, and CD117 in gastrointestinal tract endocrine tumors. Immunohistochemical studies of p16, p53, and CD117 were performed in 57 gastrointestinal tract endocrine tumors, including 22 poorly differentiated endocrine carcinomas (PDECs) and 35 well-differentiated endocrine tumors (WDETs). Overexpression of p16 and p53 was observed in 16 (73%) and 10 (45%) of the PDECs, respectively, whereas only 1 WDET showed overexpression of p53 and none showed overexpression of p16. A total of 18 (82%) of the PDECs showed overexpression of p16 or p53 proteins. This is closely associated with PDEC (P < .0001). By using overexpression of p16 or p53 as the criteria for PDEC, the sensitivity and specificity are 81.8% and 97.1%, respectively, with positive and negative predictive values of 94.7% and 89.5%, respectively. CD117 was not detected in any of the 57 gastrointestinal endocrine tumors by immunohistochemical analysis.