Recent proteomic studies identified Transferrin (Tf) as a potential biomarker for cancer. We examined the efficacy of the newly developed Tf dipstick for detecting colorectal cancer and premalignant lesions, and compared that to Immuno Fecal Occult Blood test (IFOBT). Fecal samples from 110 patients including 40 colorectal cancer, 36 premalignant subjects (including 16 with high-risk adenomas and 20 with ulcerative colitis), and 34 low-risk subjects were collected before colonoscopic examination. Compared with IFOBT, Tf had a significantly higher positive rate in patients with colorectal cancer and premalignant lesions (76% for Tf versus 61% for IFOBT, respectively; chi(2) = 4.38; P < 0.05). The difference of positivity was mainly observed in patients with premalignant lesions (72% for Tf versus 44% for IFOBT; chi(2) = 5.71; P < 0.05), whereas the positive rates in cancer group and in low-risk group were similar (both P > 0.05). Combining Tf with IFOBT together (either/or) had 90% positive rate in cancer patients, 78% in premalignant patients, and 29% in low-risk subjects. The overall accuracy of IFOBT and Tf tests for detecting colorectal cancer and premalignant lesion was 69.0% and 76.4%, respectively. Tf dipstick test seems to be a highly sensitive test for detecting not only cancer, but also premalignant lesions, and provides an additional tool for colorectal cancer screening.