The risk of carcinoma increases in patients with a 10-year or longer duration of ulcerative colitis (UC). To search for a more objective parameter to assess epithelial dysplasia. The study comprised 25 cases of longstanding UC: 7 cases with regenerative atypia, 7 with low grade dysplasia, 7 with high grade dysplasia, and 4 cases indefinite for dysplasia. The colonic biopsies obtained during endoscopy were stained with H&E to identify the aforementioned categories. Seventy-five sections from biopsy specimens were stained immunohistochemically to detect differences in the frequency and pattern of nuclei positive for the proliferation marker Ki67 and p53. In high grade dysplasia, the distribution of Ki67 positive cells was diffuse throughout the full length of the crypt, whereas low grade dysplasia and epithelium indefinite for dysplasia, as well as regenerative epithelium, showed an expanded basal zone. None of the regenerative atypia cases showed strong intensity p53 staining compared to dysplasia cases. None of the high grade dysplasia cases showed restricted p53 staining to the lower two thirds of the crypt. All the cases of HGD showed extension of Ki67 and p53 staining above the basal two thirds of the crypt. Ki67 and p53 immunostained cell assessment combined with routine histological evaluation of colorectal mucosa can improve the diagnostic accuracy, as well as the assessment of malignant transformation risk.