Two cases of ulcerative colitis (UC)-associated carcinoma or dysplasia and morphologically non-neoplastic mucosa with p53 protein overexpression ((MNNM-p53OE) were selected. DNA was extracted from the paraffin blocks of these lesions and exons 5-8 of the p53 gene were analyzed by PCR and direct sequencing, In addition, mutations in K-ras codon 12 were analyzed by PCR-RFLP methods, MNNM-p53OE was located surrounding and adjoining a coexisting carcinoma and/or dysplasia. A p53 mutation was detected in 12/22 (54.5%) MNNM-p53OE samples, 4/8 (50%) dysplasia samples and 8/8 (100%) carcinoma samples. The p53 mutations detected in MNNM-p53OE were identical to those demonstrated in the adjoining carcinoma and/or dysplasia. No K-ras codon 12 mutation was detected in ang of the samples. These results indicate that MNNM-p53OE mag share an identical clonal linkage with a coexisting carcinoma and/or dysplasia, and may be an initial and submorphological form of UC-associated neoplasia, Recognition of MNNM-p53OE in biopsy specimens may help to identify patients with UC at risk of developing colorectal carcinoma.