Patients with long-standing extensive ulcerative colitis have an increased risk of colorectal cancer compared with the general population, and the carcinoma is frequently preceded by dysplasia. Molecular markers such as Ki-67, DPC-4, and DYS nuclear matrix proteins may potentially be useful for further refining the diagnosis of dysplasia, or may even eventually provide an alternative method of predicting colorectal cancer. If DYS nuclear matrix proteins prove to be reliably restricted to dysplasia and cancer, their identification in tissues or even serum could be immensely useful. Clinical studies provide further support to the increasingly prevalent recommendation that any dysplasia warrants colectomy. Chemopreventive methods, such as supplementation with folic acid, may help reduce the incidence of neoplasia, but more studies are needed.