Prophylactic radiation to the contralateral uninvolved testicle has become a standard practice in the treatment of primary testicular lymphoma. While it is generally felt to be very effective, its failure rate is unknown. We describe a patient with primary testicular diffuse large B-cell lymphoma, who developed recurrent disease in the contralateral testicle despite receiving prophylactic testicular radiation, central nervous system prophylaxis, and anthracycline-based chemo-immunotherapy. Review of the literature shows that the testicular failure rate after prophylactic radiation may be unexpectedly high at 10% or more. We put forward hypotheses on testicular relapse and discuss potential alternative preventive strategies.