Collagenous colitis is a form of microscopic colitis that results in chronic watery diarrhea. The disorder predominantly affects middle-aged women, and its course tends to be benign. It is not thought to be a precursor of overt inflammatory bowel disease; however, apparent progression to ulcerative colitis has been reported on one previous occasion. We describe two further patients with symptoms and histologic features of collagenous colitis who subsequently developed ulcerative colitis. The first patient developed ulcerative colitis 13 months after diagnosis of collagenous colitis, although she gave a 23-year history of profuse watery diarrhea, which had not been adequately investigated. In the second patient, collagenous colitis was diagnosed soon after the onset of watery diarrhea, and 12 months later, progression to ulcerative colitis was documented. Both patients tested positive for perinuclear antineutrophil cytoplasmic antibody after they developed ulcerative colitis; the first patient was initially negative. In conclusion, these two cases, in addition to the one other in the literature, suggest that collagenous colitis and ulcerative colitis may represent extremes in the spectrum of inflammatory bowel disease and that collagenous colitis may evolve to ulcerative colitis. Therefore, progression to ulcerative colitis should be considered in any patient with known collagenous colitis whenever bloody diarrhea occurs, or if red cells, as well as white cells, are noted on stool microscopy.