We describe a rare case of intestinal amebiasis of unknown source, in an immunocompetent patient with no risk factors. The detection of an autochthonous Entamoeba histolytica strain causing ulcerative colitis (UC) in a healthy individual was unexpected, but it was the second time it had occurred in Italy in a few months therefore, it highlighted the urgency to establish a new approach in the diagnosis of UC and more generally in the diagnosis of inflammatory bowel disease, involving routine parasitological investigation even in a non-endemic area.