Hemangioblastomas are low-grade, capillary rich neoplasms of the cerebellum and spinal cord that can occur sporadically or in the setting of Von Hippel-Lindau syndrome. The present study analyzed the utility of proliferation potential in differentiating hemangioblastoma from RCC metastatic to the central nervous system using a MIB-1 (Ki-67) labeling index and assessment of expression of the RNA component of telomerase. Immunohistochemical analysis for epithelial membrane antigen (EMA) and MIB-1 was performed on paraffin-embedded sections of 27 hemangioblastomas and 5 RCC metastatic to the central nervous system. All but one hemangioblastoma demonstrated low or negative MIB-1 immunoreactivity, while 4 of 5 RCC metastases had moderate or high labeling indices. Telomerase RNA expression was assessed in 10 hemangioblastomas and in all 5 metastatic RCC by in Situ hybridization. All 10 hemangioblastomas demonstrated a lack of expression of telomerase RNA, while all 5 metastatic RCCs showed moderate to strong expression. Our results suggest that the MIB-1 labeling index is useful in differentiating hemangioblastoma from metastatic RCC and assessment of telomerase expression can also provide novel information on the difference in growth potential of these tumors.