To determine the significance of different types of cell groups in voided urine for diagnosing transitional cell carcinoma (TCC). We reviewed voided urine specimens, with corresponding biopsies taken within 120 days after urine collection, for cell groups. Type and number of cell groups were correlated with the histologic diagnoses. Of 5,001 voided urine specimens, 134 (3%) had corresponding biopsies. Flat sheets were significantly more common in urine specimens with corresponding negative biopsies (24%) than in those with biopsies showing TCC (6%) (chi 2 P = .0032). The incidence of collared, three-dimensional cell groups was low (0-7%) and not associated with biopsy findings. Irregular, three-dimensional cell groups were more common than collared cell groups and were most common in cases with invasive TCC on biopsy (38%). While this was statistically significantly more common than in urines associated with negative biopsies (17%) (chi 2 P = .0499), it was not specific. Requiring three or more irregular cell groups did not improve discrimination between TCC and benign cases. Cell groups of any type or number were not more common in cases associated with grade 1 papillary TCC than negative biopsies. Diagnoses associated with multiple irregular, three-dimensional cell groups and a negative biopsy included medullary sponge kidney, hemorrhagic cystitis, cystitis not otherwise specified, and urolithiasis. Irregular, three-dimensional cell groups were most common in voided urine from patients with invasive TCC, but the identification of cell groups of any type in voided urine had little diagnostic utility.