In the united States, nearly all cases of bladder cancer are of the transitional cell type, and epidemiological evidence indicates that among these, approximately 80% present initially as more or less well-differentiated, superficial papillary neoplasms with a tendency for multifocal or diffuse involvement of the urothelial surface and/or recurrent tumor episodes, but with limited potential for invasive growth or a lethal outcome. Bladder tumors with lethal potential generally begin as poorly differentiated, sessile growths that are usually invasive at first diagnosis. Carcinoma in situ is a change that must be elicited among intact surface cells before progressive proliferation results in a tumor mass. Evidence for such an association is both temporal and spatial. Since most transitional cell carcinomas begin as well-differentiated tumors. i.e., resembling normal urothelium, recognition of early neoplastic alteration before a papillary structure forms is unlikely and most of the evidence is spatial based upon urothelial changes adjacent to papillary tumors. The morphologic definition of carcinoma in situ is arbitrary and generally defined as a total replacement of the urothelial surface by cells which bear morphologic features of carcinoma, but which lack architectural alteration other than an increase in the number of cell layers, i.e., a flat lesion. The Union Internatiaàle Contra Cancer/American Joint Committee on Cancer (UICC/AJCC) staging scheme for bladder cancer distinguishes non-invasive papillary growths as Ta and carcinoma in situ as Tis. Because detection of carcinoma in situ, either by cytology or biopsy, depends upon recognizable malignant morphologic characteristics, studies of the lesion tend to be limited to the higher grade or more anaplastic examples. Carcinoma in situ may exist in the urothelium adjacent to a papillary or invasive bladder cancer in which case the term “concomitant” has been used. If at initial presentation the bladder cancer is detected while still entirely in situ, the term “primary” carcinoma in situ is used. Primary carcinoma in situ tends to be more indolent than the concomitant type. The lesion is usually widespread in the urothelium, and can involve the epithelium of the distal ureters, Brunn nests in the lamina propria, and the periurethral prostatic ducts and glands. Static image cytometry with DNA analysis has indicated that the cells of primary carcinoma in situ differ from muscle invasive transitional cell carcinoma by exhibiting a considerably greater nuclear DNA content. © 1992 Wiley-Liss, Inc.