Selective internal radiation therapy (SIRT) using Yttrium microspheres is a novel therapeutic approach to the localized treatment of hepatic tumors. It provides a distinct advantage over conventional external beam radiation in that its targeted nature allows the directed delivery of high doses of radiation to tumors while sparing the surrounding uninvolved hepatic parenchyma. Numerous studies have evaluated the safety and efficacy of SIRT, and it has been used to treat both primary and metastatic hepatic malignancies. However, SIRT is not without risk of complications, and has been known to cause various toxicities due to extrahepatic SIRT microsphere deposition. Reports of such injury have been only sparsely described in the pathology literature to date, and surgical pathologists therefore remain largely unaware of this phenomenon, which can potentially lead to misdiagnosis. Herein, we review the histopathology and pathophysiology of extrahepatic SIRT microsphere migration as a cause of iatrogenic tissue injury, highlighted by 3 examples of gastritis and 1 case of cholecystitis.