Objectives This study was designed to evaluate the clinical relevance of the World Health Organization (WHO) and tumor node metastasis (TNM) classifications in patients affected by pancreatic endocrine tumors. Methods Data from 76 consecutive patients with pancreatic endocrine tumors who underwent surgery were analyzed. Results Well-differentiated tumors were observed more frequently (57.9%) than well or poorly differentiated carcinomas (26.3% and 15.8%, respectively). The TNM stage was I in 27.6%, II in 39.5%, III in 19.7%, and IV in 13.2%. Univariate analysis of disease-specific survival showed that patients with stages I-II had a significantly better survival rate than those with stages III-IV (hazard ratio (HR), 12.46; 95% confidence interval (CI), 1.53-101.32; P = 0.018; HR, 25.74; 95% CI, 3.07-216.07; P = 0.003, respectively). Regarding the WHO classification, poorly differentiated carcinomas had the worst prognosis (HR, 79.13; 95% CI, 9.99-626.60; P < 0.001). Multivariate Cox regression analysis of disease-specific survival showed that the WHO classification is the only independent factors of improved survival: both poorly and well-differentiated carcinomas had an increased risk of death compared with WDTs (HR, 100.42; 95% CI, 12.16-829.40; P < 0.001; HR, 10.73; 95% CI, 1.12-104.17; P = 0.040, respectively). TNM classification and the WHO system are highly correlated (P < 0.001). Conclusions TNM stage and the WHO classification seems to be equally reliable, even if TNM classification tends to understage the patients classified using the WHO system.