Primary testicular lymphoma is a rare lymphoma entity, yet it is the most common testicular malignancy among elderly men. The majority of the cases represent non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL) with aggressive clinical behavior and a relatively high relapse rate. Due to the rareness of the disease, no randomized clinical trials have been conducted and the currently recognized standard of care is based on retrospective analyses and few phase II trials. During recent years, the tumor microenvironment (TME) and tumor-related immunity have been the focus of many tumor biology studies, and the emergence of targeted therapies and checkpoint inhibitors has significantly modulated the field of cancer therapies. Testicular DLBCL (T-DLBCL) is presented in an immune-privileged site of the testis, and the roles of NF-κB pathway signaling, 9p24.1 aberrations, and tumor-infiltrating immune cells, especially immune checkpoint expressing lymphocytes and macrophages, seem to be unique compared to other lymphoma entities. Preliminary data on the use of immune checkpoint inhibitors in the treatment of T-DLBCL are promising and more studies are ongoing.