Colorectal cancer screening is a high public health priority in all industrialized countries. However, the low sensitivity of the common guaiac screening test (HemoccultII) makes practitioners and public health decision makers reluctant to set up a national screening program. In recent years, immunochemical tests based on the use of a specific antibody have been found to be more sensitive than the HemoccultII test. However, for screening purposes, any gain in sensitivity is of interest only if specificity and positive predictive value are satisfactory. Our aim was to assess the performance of an immunochemical test with an automated reading technique (Magstream 1000) for different hemoglobin content cut‐off points. The study was carried out in the general population aged 50–74 years in the geographic area of Cotentin (Normandy, France). From 1 January 2001 to 31 December 2002, 7,421 one‐time screening tests (Magstream) were administered by general practitioners and occupational physicians to patients at the end of regular consultations. Colonoscopy was proposed to the 434 people with a positive test. All cancers occurring in the study population between 1 January 2001 and 31 December 2003 were collected by general practitioners, gastroenterologists and the local registry. At the usual positivity threshold (20 ng hemoglobin/ml), screening sensitivity and specificity at 2 years of follow‐up with 95% CIs were, respectively, 0.85 (0.72–0.98) and 0.94 (0.94–0.95). If the hemoglobin content cut‐off point had been set at 50 ng/ml instead of the usual cut‐off, positivity would have been 3.1% and positive predictive value for a cancer or a large adenoma would have been 0.49, with sensitivity of 0.68–0.83 and specificity of 0.97. Our results suggest that use of an immunochemical test with an automated reading technique could improve the prospects for mass‐screening for colorectal cancer since it offers a promising alternative to guaiac tests. © 2005 Wiley‐Liss, Inc.