Prediction of behavior in pancreatic endocrine tumors (PETs) is reliant on clinicopathologic features. However, there remains a cohort of PETs that behave aggressively despite showing indolent pathologic features. Recently, it has been suggested that CK19 and CD99 are sensitive ancillary markers that predict outcome in PETs. An analysis of 54 PETs and 2 resected liver metastases was undertaken to examine the relationship of CK19 and CD99 and the pathologic criteria in the WHO classification of PETs. CK19 was found to correlate with mitotic count (>5/50 high-power fields), an MIB-1 labeling index of > or =2%, lymphovascular/perineural permeation, lymph node involvement, and liver spread. Although not statistically significant, CK19-negative tumors tended to be smaller than the average tumor size in the series (2.5 vs. 3.6 cm). CD99 did not show any significant correlation with any of the WHO criteria. Tumors that are confined to the pancreas with low mitotic count and MIB-1 labeling index, tended to be CD99-positive. Both CK 19 (negative) and CD99 (positive) correlated with insulin-positive PETs. In conclusion, CK 19 may prove to be a useful ancillary diagnostic test in the routine work-up of PETs. CD99 does not appear to be as useful. There is no compelling evidence, from our study, to suggest that both these markers may be used in concert to predict the behavior of PETs.