Decamethylcyclopentasiloxane (D5) is a cyclic siloxane used in the production of industrial and consumer products. Four groups of 60 Fischer-344 female rats were analyzed for uterine endometrial adenocarcinoma (inhalation study with exposure levels in ppm/number of observed cases: 0/0, 10/1, 40/0, and 160/5) by exact regression (logistic, Poisson), the max poly-3 trend test, and a random effects probit model. When comparing the 160 ppm group to controls after 24 months, the incidence of adenocarcinomas was elevated (borderline significant); it was significant when all exposure levels were included. Four sets of (historical) control groups were formed, with varying heterogeneity. The effect of D5 was either significant or borderline significant when comparing all control sets to the 160 ppm group. When considering all exposure groups using any of the analysis methods, a significant effect was observed when the high dose group was included in the analysis; the effect was not significant when the high dose group was not included. The evidence tends to support the conclusion that D5 at the highest dose level (160 ppm) results in an increased incidence of adenocarcinomas. However, it is important to verify any potential effect through a biological investigation.