Paraneoplastic cerebellar degeneration (PCD) is a rare nonmetastatic complication of a carcinoma. It is typically mediated by antibodies generated against tumor antigens. These antigens are the same proteins as expressed on Purkinje cells within the cerebellum; immune activation in the central nervous system (CNS) results in the syndrome. A 56-year-old woman with stage IIIC serous ovarian carcinoma diagnosed 3 years prior developed progressive limb ataxia. Serum anti-Yo antibodies were positive, confirming the diagnosis of PCD. Treatment with plasmaphoresis, intravenous immune globulin, and immune modulation with corticosteroids and tacrolimus was unsuccessful. Although the syndrome can be debilitating and treatment options are limited, it may also be an example of a successful host immune response in certain cases.