Differentiation between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) can be complex as their symptoms are often similar and unspecific. Fecal biomarkers could be useful to select patients with suspected organic diseases for colonoscopy, with the aim to improve early diagnosis and to avoid unnecessary invasive studies. Fecal calprotectin (FC) is a protein found mainly in neutrophils that is released into the feces as a result of cell disruption and apoptosis. Currently, FC is a simple and non-invasive biomarker of intestinal inflammation. Inflammatory gastrointestinal disorders are associated with high levels of FC, as occurs in IBD. This review focuses on FC as a useful tool for differential diagnosis between IBS and IBD in adults. (AU)