Although guaiac tests have demonstrated the effectiveness of biennial fecal occult blood screening in reducing mortality from colorectal cancer, their low sensitivity poses a barrier to the widespread adoption and success of colorectal cancer screening. Laboratory studies have long shown that immunological tests can be more sensitive and specific than guaiac tests in detecting colorectal bleeding. Furthermore, they do not require any dietary restrictions. The automation of test interpretation, which makes their detection costs comparable to those of guaiac tests, now makes it feasible to consider their use in large asymptomatic populations. This automation allows for better standardization of interpretation and significantly reduces the percentage of unreadable tests compared to guaiac tests. Finally, and most importantly, quantitative interpretation of the test allows for the selection of a positivity threshold that provides the best balance between sensitivity and specificity. Comparative studies conducted in the general population show that, thanks to a judicious choice of the positivity threshold, the use of these tests in screening programs would now allow the population to be offered screening that is both more sensitive and more specific than with guaiac tests, at a reasonable cost to society. (R.A.)