The Wnt/beta-catenin pathway plays an important role in initiation in most, if not all, colon cancers. Prior work has provided important insights into the regulation of beta-catenin stability in the cytoplasm; however, relatively little is known about the mechanism by which beta-catenin activates gene transcription in the nucleus. Using genetic approaches, studies in human colon cancers and Drosophila have identified CDK8 as a colon cancer oncogene that regulates beta-catenin transcriptional activity. These convergent observations provide new insights into the regulation of nuclear beta-catenin activity and identify a novel therapeutic target for beta-catenin-driven malignancies.