Chemoprevention is a practical approach to reduce the risk of various cancers including colorectal cancer (CRC). The goal is to reduce the incidence of pre-neoplastic adenomatous polyps and prevent its progression to CRC. Curcumin and silibinin prevent intestinal polyp formation in mice. Curcumin sensitizes silymarin to exert synergistic anticancer activity in colon cancer cells. Patients presenting with multiple colorectal adenomatous polyps (MCRA) have a high lifetime risk for CRC. We present a 57-year-old man with MCRA, without deleterious germline APC or MYH mutations. Our patient had 54 polyps in the first colonoscopy, most of 3 to 8 mm and one of 20 mm with high grade dysplasia / adenocarcinoma. Four subsequent colonoscopies showed continuous development of adenomatous polyps treated by polypectomy for the most part and some with heat. After the treatment with curcumin for 3 months and a half followed by silibinin for 9 months, we find many less polyps than in the previous colonoscopies, going from the finding of 40 adenomas of 3-6 mm in the pre-treatment colonoscopy to 3 polyps after treatment.