We described an overview of the genes that are recurrently mutated in PCNSL, including (i) genes previously known to be mutated in PCNSL, such as MYD88, CD79B, PIM1 and TBL1XR1; (ii) genes altered by somatic mutations in other B cell malignancies that have not yet been reported in PCNSL, such as ETV6, IRF4 or EBF1; and (iii) genes that are altered in solid tumors, such as IRF2BP2. These results reveal the genetic heterogeneity of this disease and highlight the major signaling pathways that are deregulated in PCNSL. Here, ETV6 is linked to primary central nervous system lymphoma.