Primary central nervous system lymphoma (PCNSL) is a rare disease. A small number of cytogenetic studies of PCNSL have been conducted and several reports have been published on associated molecular and protein expression data. We combined these approaches in a series of eight PCNSL cases, analyzing the chromosomal abnormalities using comparative genomic hybridization (CGH), testing for Epstein Barr virus (EBV) involvement by in situ hybridization for EBER, assessing expression of p53, Bcl-2, Bcl-6 and CD10 by means of immunohistochemistry, and screening for mutations of the TP53 gene by DGGE. TP53 gene mutations and EBV expression were not detected. Most of the cases showed p53, Bcl-6 and Bcl-2 protein expression. CGH revealed DNA copy number changes in all eight cases. The most frequent changes were gains of chromosome 12 (63%), chromosome 18 (50%) and 20q (38%), and loss of chromosome arm 6q (75%). No correlation between protein expression and chromosomal abnormalities was found in these eight cases. Although gains of chromosome 12, 18 and 20q and loss of 6q have also been reported in systemic diffuse large B-cell lymphomas, the frequency of 6q deletion is clearly higher in PCNSL. This creates a similarity to primary lymphomas of the testes that also frequently have deletions of 6q. This suggests that suppressor genes located on chromosome 6q may play a role in the development of lymphomas at immunoprivileged sites, like the CNS.