Colorectal cancer is the second leading cause of cancer death in developed countries. There is a need for better preventive strategies to improve the outcome of this disease. The increasing availability of high-throughput methodologies opens up new possibilities for screening new markers. The application of NMR metabolic profiling to fecal water extracts has interesting potential as a diagnostic tool for detecting colorectal cancer. We obtained NMR metabolic profiles of fecal water extracts from patients with colorectal cancer and healthy individuals, to characterize possible differences between them and to identify potential diagnostic markers. Our results show that metabolic profiling of fecal water extracts is a cheap, reproducible and effective method for detecting colorectal cancer markers and therefore complements other stool-screening methods. A low concentration of short-chain fatty acids, such as acetate and butyrate, previously associated with the development of colorectal cancer, appears to be the most effective marker. Concentrations of proline and cysteine, which are major components of most colonic epithelium mucus glycoproteins, also display significant changes in samples from colorectal cancer. Differentiation between fecal water extracts from controls and patients with colorectal cancer by NMR spectroscopy combined with chemometric techniques opens up new possibilities for developing new, efficient, high-throughput screening protocols. Copyright © 2008 John Wiley & Sons, Ltd.