Synchronous and metachronous tumours are frequently observed in the urinary tract and may be explained by the concept of field cancerisation, i.e. exposure to carcinogens leads to independent transformation of many urothelial cells resulting in genetically unrelated tumours. However, increasing evidence supports the concept of clonality, i.e. the progeny of a single transformed cell spreads through the urinary system resulting in genetically related tumours. The aim of this study was to review the molecular biological evidence for both concepts and to assess the consequences of a clonality assumption on the incidence of urothelial cell carcinoma (UCC). In total 1198 non-invasive and 1113 invasive (> or = T1) UCCs of the bladder were registered as incident tumours in 1996-1997 by three Dutch cancer registries following the current registration rules of the International Association of Cancer Registries (IACR). Assuming clonality, the number of non-invasive and invasive bladder UCCs decreased by 10.9% and 11.5% respectively. A decline of 8.5% and 9.5% was found for UCCs of the ureter and renal pelvis, respectively. Current registration rules have substantial impact on the incidence estimates of UCC. New insights into the molecular biology of UCC should be translated into registration rules.