Microscopic colitis is the most common cause of chronic watery diarrhea, with normal mucosal appearance during colonoscopy. The diagnosis is made by pathological examination of biopsy specimens showing colitis with normal architecture of the mucosa. The two most frequent forms of microscopic colitis are lymphocytic colitis and collagenous colitis, but other atypical variants have been described. We report a case of lymphocytic colitis with multinucleated large cells and we discuss a variant of giant cells microscopic colitis.