Anti-Yo (type I) autoantibodies reactive with Purkinje cell cytoplasmic antigens of 34 and 62 kd are found in the serum and cerebrospinal fluid of patients with paraneoplastic cerebellar degeneration associated with cancer of the ovary, uterus, adnexa, or breast. Anti-Yo antibody response is rarely associated with other tumors. Here, we present a patient who developed paraneoplastic cerebellar degeneration and anti-Yo antibody response in association with transitional cell carcinoma of the bladder. The presence of anti-Yo antibodies was confirmed by immunofluorescence assay and by Western blot analysis against both Purkinje cell lysates and the CDR62 fusion protein. Yo antigen was demonstrated in sections of the patient's tumor. Antibody titers fell after tumor removal. Transitional cell carcinoma should be considered in patients presenting with subacute cerebellar degeneration and anti-Yo antibody response in whom ovarian, adnexal, uterine, or breast cancer cannot be detected.