CDR2 (cerebellar degeneration-related protein 2), also referred to as Yo or CDR62, is a 545 amino acid protein that is associated with the development of paraneoplastic cerebellar degeneration (PCD). PCD, an immune-mediated syndrome, belongs to a heterogeneous group of rare paraneoplastic neurologic disorders affecting the neurological system. PCD is characterized by subacute cerebellar ataxia and occurs mainly in patients with ovarian, uterine, fallopian tube or breast cancer. Patients with ovarian or breast cancer develop an immune response against cancer cell-expressed CDR2 and Purkinje neuron-expressed CDR2. The presence of the anti-CDR2 antibody in patients with PCD symptoms warrants an aggressive approach to diagnosis and treatment of the underlying cancer.