The aims of this study were to determine the diagnostic utility of the serum levels of the soluble interleukin 2 receptor (sIL-2R) as a tumor marker of primary central nervous system lymphoma (PCNSL) and to investigate the cellular source of sIL-2R using immunohistochemical staining. The serum sIL-2R levels of 37 samples from suspected PCNSL patients were measured. There were 13 patients with PCNSL and 24 patients with other diseases such as glioma, metastatic tumor, inflammation, or cerebrovascular disease. The serum sIL-2R levels of the PCNSL cases and other brain diseases were 629.5 ± 586.0 U/ml (mean ± SD; range 189-2220 U/ml) and 408.5 ± 250.7 U/ml (160-837 U/ml), respectively. The serum sIL-2R levels of the two groups overlapped, and hence the difference between them was not significant. sIL-2R is the α subunit of IL-2R. It is also known as CD25, and is cleaved from its position in the cell membrane and released into the blood. CD25 expression was immunohistochemically detected in 7 of 11 PCNSL samples. Confocal laser microscopy revealed that CD25 signals were present in atypical cells and mononuclear cells. We concluded that both lymphoma cells and infiltrating T cells express CD25, which is one of the cellular sources of sIL-2R.