Objective: To compare the Hemoccult II and HemoQuant tests regarding their specificity and sensitivity in screening for colorectal neoplasia. Design: Cross-sectional study in which subjects underwent the two tests in parallel, after excluding dietary hemes and peroxidase-rich foods. HemoQuant results were analyzed for three different upper limits of normality (1.5, 2.0, 3.0 mg/g feces). Setting: A university hospital and the surrounding community. Participants: A total of 150 healthy volunteers, 124 patients with colorectal cancer, and 86 patients with adenoma. Main Outcome Measures: Blinded comparison of the specificity and the sensitivity of the two tests for colorectal cancer and adenoma. Results: Test specificity was 99.3% with Hemoccult and was 92.7%, 94.7%, and 97.3% with HemoQuant, depending on the cutoff point; differences between Hemoccult and HemoQuant were significant when cutoffs of 1.5 and 2.0 mg/g were used in HemoQuant testing (6.6% [95% CI, 2.3 to 11.1] and 4.7% [CI, 0.8 to 8.5], respectively). Test sensitivity for colorectal cancer at all sites was 89.5% with Hemoccult and was 83.1%, 74.2% and 62.9% with HemoQuant, for the 1.5, 2.0, and 3.0 mg/g cutoffs, respectively; differences were significant with the 2.0 and 3.0 mg/g cutoff points (6.4% [CI, 6.7 to 24.0] and 26.6% [CI, 17.4 to 35.9%], respectively). The two tests had similar levels of sensitivity for cancers proximal to the splenic flexure, but sensitivity was substantially lower with HemoQuant for the more distal cancers. For all adenomas, test sensitivity was 30.2% with Hemoccult and ranged from 45.4% to 22.1% with HemoQuant. Conclusions: Although HemoQuant provides a precise measurement of fecal heme and its porphyrin degradation products, the test's performance characteristics in the detection of colorectal neoplasia are less satisfactory than those of Hemoccult II, a qualitative test for the presence of heme.