In contrast to CSF, serum is a less suitable means for monitoring disease activity, as plasma-derived cell-free DNA was found not to harbor somatic mutations of the MYD88 and CD79B driver genes in newly diagnosed PCNSL when blood was collected prior to neurosurgery, i.e., without traumatic blood–brain barrier alterations that may allow the leakage of cell-free tumor DNA into the blood [21]. The gene discussed is CD79B; the disease is primary central nervous system lymphoma.