Clear cell change (CCC) in colonic adenoma is rare, and its biological and clinical significance remains unknown. Malignant progression of an adenoma with CCC has seldom been reported. We report a case of a sigmoid adenoma with multiple foci of CCC associated with high-grade dysplasia and invasive carcinoma in a 62-year-old patient. We evaluated the histochemical and immunohistochemical characteristics of each component of the adenoma. In contrast to other parts of the adenoma, p53 was strongly and diffusely overexpressed in the areas of CCC, high-grade dysplasia, and carcinoma. The MIB-1 labeling index was also significantly higher in these components than in other parts of the adenoma. In conclusion, our findings suggest that CCC in adenoma may be associated with malignant progression of the adenoma. Hence, for practical purposes, we recommend considering CCC in colonic adenomas as a high-grade dysplasia equivalent and following up the patient accordingly.