BACKGROUND Colorectal cancer (CRC), the third most common cause of death in both males and females worldwide, shows a positive response to therapy and usually a better prognosis when detected at an early stage. However, the survival rate declines when the diagnosis is late and the tumor spreads to other organs. Currently, the measures widely used in the clinic are fecal occult blood test and evaluation of serum tumor markers, but the lack of sensitivity and specificity of these markers restricts their use for CRC diagnosis. Due to its high sensitivity and precision, colonoscopy is currently the gold-standard screening technique for CRC, but it is a costly and invasive procedure. Therefore, the implementation of custom-made methodologies including those with minimal invasiveness, protection, and reproducibility is highly desirable. With regard to other screening methods, the screening of fecal samples has several benefits, and metabolomics is a successful method to classify the metabolite shift in living systems as a reaction to pathophysiological influences, genetic modifications, and environmental factors. OBJECTIVE To characterize the variation groups and potentially recognize some diagnostic markers, we compared with healthy controls (HCs) the fecal nuclear magnetic resonance (NMR) metabolomic profiles of patients with CRC or adenomatous polyposis (AP). METHODS Proton nuclear magnetic resonance spectroscopy was used in combination with multivariate and univariate statistical approaches, to define the fecal metabolic profiles of 32 CRC patients, 16 AP patients, and 38 HCs well matched in age, sex, and body mass index. RESULTS NMR metabolomic analyses revealed that fecal sample profiles differed among CRC patients, AP patients, and HCs, and some discriminatory metabolites including acetate, butyrate, propionate, 3-hydroxyphenylacetic acid, valine, tyrosine and leucine were identified. CONCLUSIONS In conclusion, we are confident that our data can be a forerunner for future studies on CRC management, especially the diagnosis and evaluation of the effectiveness of treatments.