Endoglin (CD105) is predominantly expressed on the cellular lineages within the vascular system and it is overexpressed on proliferating endothelial cells that participate in neoangiogenesis, with a weak or negative expression in the vascular endothelium of normal tissues. To investigate the correlation between the CD105 expression and possible prognostic markers or progression in the primary central nervous system lymphomas (PCNSLs), the present study assessed 26 cases of PCNSL by immunostaining for CD105 and CD34. Intratumoral microvessel density (IMVD) was determined in the hotspots and interfaces at a magnification of x200. According to the mean value, the patients were classified into lower-IMVD and higher-IMVD groups. When CD34 was used as a marker of angiogenesis, the survival rates of these two groups demonstrated no significant difference. In contrast, when CD105 was used as a marker of angiogenesis, the survival rate of the lower-IMVD group was significantly higher than that for the higher-IMVD group (P < 0.01). In the group of CD34-immunostained vessels, no difference was observed in IMVD between the hotspots and interfaces (P = 0.31). In the group with CD105-immunostained vessels, a greater IMVD was observed in the hotspots than in the interfaces (P < 0.01). These results suggested that the growth of PCNSLs was dependent on angiogenesis, that IMVD as determined by anti-CD105 monoclonal antibody was a reliable prognostic marker in PCNSLs, and that PCNSLs may therefore not require sufficient neoangiogenesis at the start of PCNSLs, however, it may instead require a higher rate of neoangiogenesis as they infiltrate and destroy the brain parenchyma.