Differentiation of primary central nervous system lymphoma (PCNSL) from glioblastoma using arterial spin labeling perfusion and diffusion tensor imaging (DTI). We performed a prospective study of 31 patients with a provisional diagnosis of PCNSL and glioblastoma who underwent conventional magnetic resonance imaging, DTI, and arterial spin labeling of the brain. The tumor blood flow (TBF), mean diffusivity (MD) plus fractional anisotropy (FA) of the mass were measured. The final diagnosis was confirmed by pathological examination. The TBF of PCNSL (26.41 ± 4.03 mL/100 g/minute) was significantly lower than that of glioblastoma (51.08 ± 3.9 mL/100 g/minute; P= 0.001). The TBF cutoff (35.73 mL/100 g/minute) used for differentiation showed area under the curve (AUC) of 0.93, accuracy of 95.2%, sensitivity of 91.7%, and specificity of 100%. The MD of PCNSL (0.87 ± 0.2X 10-3 mm2/second) was significantly lower than that of glioblastoma (0.87 ± 0.2× 10-3 mm2/second; P= 0.01). The MD cutoff (0.935× 10-3 mm2/second) used for differentiation showed an AUC of 0.73 and accuracy of 66.7% and a sensitivity of 75% and specificity of 55.6%. The FA of PCNSL (0.253 ± 0.05) was significantly greater than that of glioblastoma (0.135 ± 0.06; P= 0.001). The FA cutoff (0.185) used for differentiation revealed an AUC of 0.944 and accuracy of 85.7% and a sensitivity of 83.3% and specificity of 88.9%. The combined TBF, MD, and FA cutoffs revealed an AUC of 0.96 and accuracy of 95.5% and a sensitivity of 83.3% and specificity of 100%. The noninvasive imaging parameters using TBF and DTI might help in differentiating PCNSL from glioblastoma.