Segmental renal resection and improved endourological techniques have resulted in conservative treatment options for transitional cell carcinoma of the renal pelvis. These techniques have increased the need for more objective measures of biological behavior. We applied two immunohistochemical markers of cellular proliferation, proliferating cell nuclear antigen (PCNA; PC10) and Ki-67 (MIB-1), to 58 archival cases of renal pelvic transitional cell carcinomas and correlated the percentage of positive cells to grade, stage, and survival, and to one another; mitotic counts (mitoses/10 high-power fields) were also performed. Expression of PCNA showed a significant difference between grades 1, 2, and 3 tumors (P = 0.05) and between superficial (Ta, T1) and invasive tumors (T2-4) (P = 0.02). There was a significant overlap, however, in the percentage of cells staining between the grades as well as the stages. PCNA staining did not correlate with survival and did not identify a subset of patients with low-stage, low-grade tumors with a poorer prognosis. The Ki-67 score exhibited a stronger correlation with grade (P = 0.001), and there was a trend of increasing Ki-67 expression with higher stage tumors, but this did not reach statistical significance (P = 0.10). Ki-67 showed comparable findings to PCNA with regard to survival and overlap in staining between the grades and stages. Mitotic counts did correlate with grade (P = 0.003) but not stage or survival. This study demonstrates that cellular proliferation, as determined by the immunohistochemical markers, Ki-67 and PCNA, is related to grade and, to a lesser extent, stage, but the use of these markers as measures of biological behavior in clinical practice may be limited.