Colorectal cancer (CRC) can be prevented by screening programs in the population at average risk (men and women aged between 50 and 74 years) and at high risk (first degree relatives, CRC hereditary syndromes and chronic inflammatory bowel disease). Early CRC (with submucosal invasion) and advanced adenomas (size > or =10mm, with severe dysplasia or >20% villous component) produce intermittent microscopic blood losses that can be detected through chemical and immunological testing for fecal occult blood (C-FOBT and I-FOBT). Among the screening strategies in the population at average risk, annual or biannual fecal occult blood testing is the most widely used due to its non-invasiveness and low cost. Four randomized clinical trials have shown that annual or biannual screening with guaiac-based tests (C-FOBT) reduces overall mortality due to CRC by 16% and CRC incidence by 20% and 17% respectively. However, these tests have major drawbacks, especially their low sensitivity in detecting early CRC and advanced adenoma, their lack of specificity in detecting human hemoglobin (Hb), and their high fecal Hb detection threshold (>300microgHb/gfeces). In the last few years, major developments have occurred in immunological tests (I-FOBT), based on an antigen-antibody reaction that specifically detects human Hb, and these tests are currently available as an alternative to C-FOBT. Their main advantages are as follows: firstly, I-FOBT specifically detect human Hb in stools and at much lower levels (40-300microgHb/gfeces) than C-FOBT; secondly, automated analysis avoids subjectivity in reading qualitative tests and allows large population groups to be studied in a short time, making I-FOBT ideal for population-based screening; thirdly, I-FOBT fairly accurately selects individuals for colonoscopy so that approximately half of patients with an I-FOBT test show clinically significant colorectal neoplasia (advanced adenoma or invasive CRC); fourthly, the cut-off point for fecal Hb detection can be modified, depending on the availability of endoscopic resources; fifthly, when cut-off points for fecal Hb of 50-150microgHb/gfeces are used, more than twice the number of CRC and advanced adenomas are detected than with C-FOBT, with a reasonable false-positive rate; and sixthly, I-FOBT are better accepted by the population due to their simplicity and ease of use, increasing participation in screening programs. For all these reasons, the current recommendation is that the new quantitative I-FOBT tests replace C-FOBT tests when the strategy of population-based screening through annual or biannual fecal occult blood testing is considered.