Although colorectal cancer screening is cost-effective, it requires a considerable net investment by governments or insurance companies. If screening was cost saving, governments and insurance companies might be more inclined to invest in colorectal cancer screening programs. We examined whether colorectal cancer screening would become cost saving with the widespread use of the newer, more expensive chemotherapies. We used the MISCAN-Colon microsimulation model to assess whether widespread use of new chemotherapies would affect the treatment savings of colorectal cancer screening in the general population. We considered three scenarios for chemotherapy use: the past, the present, and the near future. We assumed that survival improved and treatment costs for patients diagnosed with advanced stages of colorectal cancer increased over the scenarios. Screening strategies considered were annual guaiac fecal occult blood testing (FOBT), annual immunochemical FOBT, sigmoidoscopy every 5 years, colonoscopy every 10 years, and the combination of sigmoidoscopy every 5 years and annual guaiac FOBT. Analyses were conducted from the perspective of the health-care system for a cohort of 50-year-old individuals who were at average risk of colorectal cancer and were screened with 100% adherence from age 50 years to age 80 years and followed up until death. Compared with no screening, the treatment savings from preventing advanced colorectal cancer and colorectal cancer deaths by screening more than doubled with the widespread use of new chemotherapies. The lifetime average treatment savings were larger than the lifetime average screening costs for screening with Hemoccult II, immunochemical FOBT, sigmoidoscopy, and the combination of sigmoidoscopy and Hemoccult II (average savings vs costs per individual in the population: Hemoccult II, $1398 vs $859; immunochemical FOBT, $1756 vs $1565; sigmoidoscopy, $1706 vs $1575; sigmoidoscopy and Hemoccult II $1931 vs $1878). Colonoscopy did not become cost saving, but the total net costs of this strategy decreased from $1317 to $296 per individual in the population. With the increase in chemotherapy costs for advanced colorectal cancer, most colorectal cancer screening strategies have become cost saving. As a consequence, screening is a desirable approach not only to reduce colorectal cancer incidence and mortality but also to control the costs of colorectal cancer treatment.