The T25 single-point estimate method of evaluating the carcinogenic potency of a chemical, which is currently used by the European Union (EU) and is denoted the EU approach, is based on the selection of a single dose in a chronic bioassay with an incidence rate that is significantly higher than the background rate. The T25 is determined from that single point by a linear extrapolation or interpolation to the chronic dose (in mg/kg/day), at which a 25% increase in the incidence of the specified tumor type is expected, corrected for the background rate. Another method used to obtain a carcinogenic potency value based on a 25% increase in incidence above the background rate is the estimation of a T25 derived from a benchmark dose (BMD) response model fit to the chronic bioassay data for the specified tumor type. A comparison was made between these two methods using 276 chronic bioassays conducted by the National Toxicology Program. In each of the 2-year bioassays, a tumor type was selected based on statistical and biological significance, and both EU T25 and BMD T25 estimates were determined for that end point. In addition, simulations were done using underlying cumulative probability distributions to examine the effect of dose spacing, the number of animals per dose group, the possibility of a dose threshold, and variation in the background incidence rates on the EU T25 and BMD estimates. The simulations showed that in the majority of cases the EU T25 method underestimated the true T25 dose and overestimated the carcinogenic potency. The BMD estimate is generally less biased and has less variation about the true T25 value than the EU estimate.