Data from a small series of four patients with primary CNS lymphoma (PCNSL) and one patient with primary testicular lymphoma (PTL), for whom no standard-of-care treatment options are available, indicate the effectiveness of the anti-PD-1 antibody nivolumab. This approach was selected based upon the high frequency of 9p24.1 copy-number alterations in these patients, which are associated with increased PD-L1 expression, in addition to the effectiveness of anti-PD-1 antibodies observed in patients with other forms of lymphoma. All five patients had clinical and radiographic responses to nivolumab, and four had near-complete resolution of symptoms upon commencement of treatment. Three patients remain progression free after 13–17 months of follow-up monitoring. The authors add that this approach is now being investigated in a phase II clinical trial in patients with PCNSL or PTL.