OBJECTIVES: To evaluate cost-effectiveness of the implementation, in Colombia, of different screening strategies for colorectal cancer (CRC): fecal occult blood stool guaiac test (OB-GT), fecal occult blood immunochemical test (OB-IT), conventional colonoscopy, sigmoidoscopy, OB-GT followed by sigmoidoscopy, and OB-IT test plus sigmoidoscopy.  METHODS: We designed a Markov model representing the natural history of CRC in adult Colombians, for the whole lifespan of each individual, in one-year cycles, using local demographic and epidemiological data. This model was then modified for each of the screening strategies, assuming detection rates based on systematic review of the literature. Direct medical costs, from the Colombian health system perspective (third-party payer), were estimated using base-case data analysis from the Instituto Nacional de Cancerología (the Colombian national cancer reference center) and applying two different national tariff manuals (locally known as SOAT and ISS-2001). The costs assigned to each screening strategy included other diagnostic procedures included in standard protocols as well as therapy for pre-neoplasic or cancer therapy at different stages of the disease. A strategy was considered cost-effective if an incremental life year gained (LYG) costs up to three times the per capita GDP of US$6225. Discount rate was 3%, for costs and LYG.  RESULTS: The cost in US$ per LYG differed markedly depending on the tariff manual used. In both cases, however, biennial OB-GT was cost-effective (US$10,641 and US$2,694 per LYG), compared with annual OB-GT  (US$ 18,902 and US$27,237 per LYG), and biennial OB-IT (US$46.439 and US$14.040 per LYG). Other screening strategies were clearly not cost-effective under our assumptions. Probabilistic sensitivity analysis did not change results significantly. CONCLUSIONS: The most cost-effective screening strategy for CRC in Colombia (and the only one below our threshold) was biennial feccal occult blood guaiac test.