Seven client owned dogs with confirmed relapsed lymphoma were enrolled in a prospective feasibility study investigating the effects of low-dose total body irradiation (LDTBI) delivered in a single 1 Gy fraction. LDTBI for relapsed lymphoma was safe and well tolerated. The only major side-effect of LDTBI was asymptomatic thrombocytopenia in all dogs. The median platelet nadir was 17 000/μL (range 4000–89 000), which occurred a median of 10 days (range 8–30) post irradiation. Three dogs had short-term partial responses, two stable disease and two progressive disease (PD). Six dogs were euthanatized for PD, and one dog died while in partial remission. No dogs had clinical complications. Survival analysis was not performed, because the study design did not allow for evaluation of survival time. Larger studies incorporating LDTBI in the induction/consolidation phase of treatment need to be performed to determine the therapeutic efficacy of LDTBI.