Malignant bladder neoplasms of urothelial origin are rare among children; fewer than 125 cases have been reported. Typically, these tumors are single papillary lesions of low grade and stage that have an excellent prognosis following surgical excision. A grade III transitional cell carcinoma of the bladder occurred in a 14-year-old boy who had no urinary tract malformation, carcinogenic exposure, or family history of cancer. Immunohistochemical stains of the tumor were positive for cytokeratin and high-molecular-weight keratin. The tumor tissue failed to stain with an antibody to the patient's blood group [anti-ABO(H)] but was positive for the Thomsen-Frieden-reich antigen. Flow cytometry of the tumor cells demonstrated a diploid or near-diploid DNA content. A karyo-type of the tumor showed a modal chromosome number of 46 with one reciprocal translocation between chromosomes 17 and 22 and a nonreciprocal translocation between chromosomes 18 and 22. The tumor was unique because of its highly aggressive nature and its diploid chromosome number. This case represents the first indepth characterization of a transitional cell carcinoma in a pediatric patient by flow cytometry and cytogenetics, as well as a variety of immunohistochemical studies including ABO(H) blood group and Thomsen-Freidenreich antigens.