An eight-year-old dog with a local relapse of an osteosarcoma was treated with partial maxillectomy and systemic radionuclide therapy that involved two injections, 43 and 45 megabecquerels per kg bodyweight of the bone-seeking agent samarium-153-ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP), 15 weeks apart. A transient drop in white blood cell count and platelet count was observed following each 153Sm-EDTMP treatment. Follow-up 21 months after surgery revealed no evidence of local recurrence or metastases. The dog was in excellent condition, suffering only minor sequelae from the surgical procedure. Compared with historical controls treated with surgery alone, the combination of surgery and systemic radionuclide therapy seems a promising strategy for the treatment of canine osteosarcoma.