In order to evaluate the usefulness of p53 immunohistochemistry (IHC) in the diagnosis of ulcerative colitis-associated colorectal carcinoma (UCACRC), ordinary paraffin sections were examined in 61 cases with ulcerative colitis (UC) and 29 control cases without UC. Among the 61 cases with UC, 11 were complicated by carcinoma coexisting with dysplasia, three with dysplasia, and two cases with adenoma. There were a total of 38 dysplasias, including 33 low grade dysplasias (LGD) and five mixed low and high grade dysplasias (LGD + HGD). The results of p53 IHC were divided into diffuse, nested, scattered and sporadic patterns for 29 control cases. Diffuse and nested patterns were presumed to reflect mutant forms of p53 protein and were defined as overexpression of p53 protein. In non-neoplastic mucosa of UC, the frequency of p53 positive tubules was significantly higher in active phase (13.5-17.9%) than in resolving phase (3.9-6.5%) and in remission (0.7-2.4%), regardless of association with neoplasia. Eight of the 37 lesions of dysplasia (21. 6%) showed p53 overexpression: 12.5% in LGD and 80.0% in LGD + HGD. The rate of p53 overexpression was significantly higher in UCACRC (90.9%) than in non-neoplastic mucosa of UC (0%), LGD and sporadic colorectal carcinoma (54.5%), but it did not differ between UCACRC and LGD + HGD. Interestingly, the mucosa without dysplasia showed p53 overexpression in one case of UCACRC. The biopsy specimen taken 4 years before the diagnosis of carcinoma revealed p53 overexpression in another case with UCACRC. These results suggest that p53 abnormalities play an important role in UC-associated tumorigenesis in its relatively early phase. For the diagnosis of dysplasia and carcinoma in UC, p53 IHC seems to be useful.