Ulcerative colitis (UC)-related intraepithelial neoplasia and its distinction from regenerative changes and sporadic adenomas occurring in UC is one of the greatest challenges in gastrointestinal pathology. Recently, the molecular changes in UC-related neoplastic progression have been determined and compared with the molecular changes in sporadic carcinogenesis. Diagnostically promising differences between sporadic and UC-related carcinogenesis are the advent of genetic changes in non-neoplastic UC-related mucosa and the early loss of 18q (harbouring SMAD2, SMAD4, and DCC) and 17p (site of p53) in UC-related tumorigenesis. These studies have given rise to a number of adjunct methods in the determination of UC-related neoplasia. Never the less, conventional histopathology still remains the gold standard in the diagnosis of UC-related neoplasia. Training of histopathologists therefore is one of the most important issues in conquering the diagnostic challenges of UC-related neoplasia. The working group "Gastrointestinal Pathology" of the German Society for Pathology set up a diagnostic multicenter trial which was open to everyone interested. The interobserver variability regarding ulcerative colitis-related neoplasia was quite promising (kappa = 0.63). A consensus diagnosis was reached for all the specimens and diagnostic criteria for UC-related neoplasia were discussed, reevaluated, and agreed on. Adjunct methods and emerging markers for the diagnosis of ulcerative colitis-related neoplasia (p53, Ki67, AMACR) and its distinction from regenerative changes and sporadic adenomas occurring in UC (ALM) will be presented and discussed.