Histone deacetylase (HDAC) inhibitors are an emerging class of targeted cancer therapeutics, and little is known about HDAC expression in gynecologic malignancies. Therefore, we tested the hypothesis whether high-level expression of class 1 HDACs (HDAC1, 2, and 3) is associated with clinically distinct subsets of ovarian and endometrial carcinomas. Expression was assessed by immunohistochemistry in a population-based cohort of 465 ovarian and 149 endometrial carcinomas and correlated with clinicopathologic parameters. Each of the HDACs was expressed at high levels in most ovarian (HDAC1, 61%; HDAC2, 93%; HDAC3, 84%) and endometrial (HDAC1, 61%; HDAC2, 95%; HDAC3, 83%) carcinomas. Further, 55% and 56% of ovarian and endometrial carcinomas, respectively, expressed all three HDACs at high levels. Such cases were less common among endometrioid subtypes of ovarian and endometrial carcinomas (36% and 52% positive cases, respectively) compared with high-grade serous subtypes (64 and 69%, respectively, P < .001). High-level expression of all three HDACs is associated with a poor prognosis in ovarian endometrioid carcinomas (hazard ratio, 6.7; 95% confidence interval, 1.9-23.3). The independent prognostic information and the overall high rate of expression for class I HDACs suggest that these targets should be explored as predictive factors in ovarian and endometrial carcinomas prospectively.