Here we review our current strategy for identifying phenotypic changes in the urothelium of bladder cancer patients with invasive disease, using a combination of proteomic technologies and immunowalking. This approach, which in principle can be applied to the study of any type of bladder cancer, makes use of proteomic technologies (for more information see http//:biobase.dk/cgi-bin/celis) to reveal and identify proteins that are differentially expressed in fresh tumors and normal urothelium. Thereafter, specific antibodies against the differentially expressed proteins are used (immunowalking) to stain serial cryostat sections of cystectomies obtained from tumor-bearing patients who have undergone removal of the bladder for invasive disease. Since bladder cancer is a field disease-that is, a large part of the bladder lining is involved-the urothelium of these patients is expected to exhibit a spectrum of abnormalities, ranging from early stages of transformation to invasive disease. Besides highlighting the problems one faces when applying powerful proteomic technologies to the study of heterogeneous biopsy material, these studies show that it is feasible to study bladder cancer under experimental conditions that closely resemble the in vivo situation.