The use of Yttrium microspheres to treat unresectable hepatoma is increasing worldwide. Therapeutically, Yttrium microspheres show promising increases in survival and tumor response, as well as acceptable toxicities. Here, we report on a 67-year-old man with hepatitis C-related advanced-stage hepatoma. This patient received selective internal radiation therapy (SIRT) using Yttrium microspheres (SIR-Spheres®). The patient displayed bone marrow suppression that resulted in a transient yet profound thrombocytopenia. To our knowledge, this is the first case of a hematologic complication as a consequence of the use of commercially available Yttrium microsphere devices.