Background: Paraneoplastic cerebellar degeneration (PCD) is a rare immune-mediated disorder often linked to gynecologic or breast tumors, with anti-Yo antibodies being a key marker. Appendiceal adenocarcinoma-associated PCD has not been previously reported.Case Report: A 64-year-old woman presented with agitation, ataxia, and disinhibition. Magnetic resonance imaging and cerebrospinal fluid were unremarkable, but serum testing revealed anti-Yo antibodies. She received high-dose corticosteroids without full neurological recovery. Positron emission tomography-computed tomography later revealed a hypermetabolic lesion in the appendix. Histopathology confirmed early-stage appendiceal adenocarcinoma. After surgical resection, both autonomic and neuropsychiatric symptoms resolved, with sustained remission at 2.5 years. Conclusion This is the first reported case of anti-Yo–associated PCD linked to appendiceal adenocarcinoma. Early recognition of PCD in atypical presentations can guide oncological investigation even when initial screening is negative. Early treatment with high-dose corticosteroid therapy in combination with early surgical resection may be curative.