The use of selective internal radiation therapy (SIRT) with SIR-Spheres(R) (Sirtex, Sydney, Australia) is increasingly recognized as a potential therapeutic modality of primary and secondary malignant liver tumors. A number of treatment-related complications have been described despite technical expertise and detailed pretreatment investigations to assess suitability. We describe a case of gastric ulceration from nontargeted deposition of SIR-spheres(R) in the gastric mucosa with life-threatening consequences. This case highlights the need for careful screening and appropriate patient selection, and the need to recognize ulceration from SIRT as a potential complication of treatment. The characteristic endoscopic, radiologic, and histopathologic findings are illustrated and recommendations are reviewed with regard to the current literature.