The aim of this study is to compare the expression pattern of matrix metalloproteinases (MMP) in primary CNS lymphoma (PCNSL) with that of nodal lymphoma (NL). PCNSL possesses a characteristic pattern of brain infiltration, specifically, perivascular aggregation and destruction of the surrounding connective tissue. Hypotheses have been proposed that this infiltration pattern indicates the infiltration of lympoma cells from outside the CNS. However, the mechanism of this infiltration pattern has not been clearly explained. Here we performed quantitative analysis of mRNA expression of MMP1, 2, 3, 7 and 9 in lymphoma cells from 10 cases of PCNSL, all of which were diagnosed as diffuse large B-cell lymphoma (DLBCL), and 14 cases of nodal DLBCL. Immunohistochemistry was also performed for phenotyping of lymphoma cells and for examining the localization of MMPs. The expression level of MMP7 in PCNSL (median ratio to normal lymophocytes, 45.6) was significantly higher than the level in NL (median, 7.55). By contrast, the expression levels of MMP2 (median, 31.7) and MMP9 (median, 1.30) in PCNSL were significantly lower than those in NL (median, 120 and 16.5, respectively). The expression levels of MMP1 and MMP3 were very low and not different between PCNSL and NL (almost comparable to those in normal lymphocytes). Immunohistochemical phenotyping revealed that the frequency of non-germinal center type DLBCL was significantly higher in PCNSL than in NL. These results, notably the significantly increased expression of MMP7 in PCNSL, suggest the involvement of this MMP in the characteristic infiltration pattern of PCNSL. They also support the existing hypothesis that PCNSL and NL are of different origins.