Occult blood in the stool can be detected by chemical (guaiac), heme-porphyrin, or immunological methods. Each has advantages and disadvantages, with the guaiac slide test Hemoccult II (SmithKline Diagnostics) remaining the most widely used. Various technical factors affect its clinical performance, most notably whether the slides are rehydrated before processing; hydration increases test sensitivity for colorectal cancer but markedly decreases specificity, resulting in a large number of false-positive reactions that require invasive and expensive colonic workup. Newer immunological tests generally have high sensitivity, but poor specificity remains an important problem. In clinical screening situations, unhydrated Hemoccult has about 50% sensitivity for colorectal cancers and about 98% specificity. Only 5% to 10% of positive reactions prove due to cancer, however, so the large majority of reactive tests are false positives; this is an important weakness of occult blood screening. Slide hydration detects more tumors, but the predictive value of a positive test for cancer drops to only about 2%, which greatly diminishes the appeal of hydration. Sensitivity of occult blood tests for benign colonic polyps is poor, and most polyps found during workup of a positive reaction are actually detected by chance because of high prevalence in the general population. Controlled clinical trials have now documented that periodic occult blood screening produces a relatively small but significant mortality benefit from colorectal cancer--about 15% to 18% for biennial testing with unhydrated Hemoccult. Aggressive annual screening with hydrated Hemoccult may lower mortality by more than 30% but at a very high cost because of poor specificity and very low predictive value. Regular occult blood testing beginning at age 50 has been endorsed by many professional organizations because of the documented mortality benefit, but poor compliance, high costs, and ethical uncertainties seriously temper its justification. Whether to implement widespread occult blood screening remains a difficult societal decision.