We here by report a case of a 42 year-old white woman with an eight-year history of watery diarrhea where the rectal biopsies performed in endoscopically normal mucosa led to the diagnosis of collagenous colitis, characterized histologically by a thickening of the colonic subepithelial basement membrane. A brief review of the current etiopathogenic concepts of this entity is done and the importance of performing rectal biopsies in patients with unexplained diarrhea and normal appearing colon mucosa is stressed. A clinical improvement following therapy with Sulfasalazine and Beta-methasone enemas was found in this patient. We discuss the current views on the therapy and the difficulties of assessing responses to drugs in this condition.