The cost-effectiveness of two colon cancer-screening strategies was compared. The first strategy mirrors the recommendations of the American Cancer Society and includes sigmoidoscopy starting at age 50, and yearly fecal occult blood testing. The second strategy is screening with colonoscopy. The analysis revealed that the 10-yr cost of screening with sigmoidoscopy is nearly $1,700, compared with nearly $2,500 for colonoscopy, using prevailing procedure costs. This difference can be reduced by lowering the cost of normal colonoscopies. The cost of identifying one patient with an adenomatous polyp is $8,766 with sigmoidoscopy, compared to $5,988 with colonoscopy because of the higher detection rate with colonoscopy. The calculated cost of preventing one death from colon cancer is $444,133 with sigmoidoscopy versus $347,214 with colonoscopy. In conclusion, colon cancer prevention with current screening methods is very costly. Screening with sigmoidoscopy and fecal occult blood testing may not be cost-effective, compared to screening with colonoscopy.