It has been claimed that CNS lymphoma, a rare neoplasm accounting for only a small fraction of malignant brain tumors, occurs with increasing frequency in immunologically normal as well as immunocompromised individuals. We investigated the prognostic value of Ki-67 index, p53, and bcl-2 oncoprotein expression in relation to the clinicopathological parameters in the primary CNS lymphoma patients. The tumors were graded by Kiel classification and the Working formulation and included 33 high-grade, 4 intermediate-grade, and 5 low-grade lymphomas. The phenotype was determined in 38 cases: 30 were B cell type and 8 were T cell type. All cases displayed variable degrees of nuclear Ki-67 staining from 1.0% to 92.0% (mean 51.1%). A highly significant correlation was established between the proportion of Ki-67 positive cells and the classification into grades (p=0.0002) and phenotypes (p=0.0002). Overexpression of p53 and bcl-2 protein was found in 37.1% and 51.4% of 35 patients, respectively. And p53 expression was significantly increased in B cell type (p=0.02). On Kaplan-Meier survival curve, the phenotype, grade of tumors, and p53 and bcl-2 protein expression were not correlated with overall survival. On multivariate analyses, overall survival was independently influenced by Ki-67 index. In conclusion, it is suggested that Ki-67 proliferating index is the most important marker for predicting biologic behavior of the primary CNS lymphoma.