The purpose of this study was to determine if metronomic administration of lomustine following palliative radiation therapy (RT) improved length of palliation and therefore survival in dogs with appendicular osteosarcoma compared to treatment with palliative radiation alone. A search of medical records identified dogs with appendicular osteosarcoma, treated with palliative RT (2 fractions of 8 Gray in a 24 hour time frame, day 0 and day 1; or day 0, 6 hours apart). Data collected included signalment, history, clinical signs, physical examination findings, clinicopathologic abnormalities, extent of disease, response, toxicity, other therapy, survival time, and whether dogs received metronomic lomustine (ML) or not. Of 86 patients, 43 received ML while 43 did not. Median survival time (MST) was not significantly different ( = 0.84), at 184 +/- 17 days for patients which received ML, and 154 +/- 20 days for those which did not. Metronomic lomustine administration was well-tolerated, but it did not improve survival in dogs with palliatively treated osteosarcoma.