Paraneoplastic optic neuropathy (PON) is a rare cause of vision loss usually associated with small cell lung cancer. Patients with this condition usually test positive for anti–collapsin response mediating protein-5 (CRMP-5). We describe a case of a 57-year-old woman with bilateral vision loss with the characteristic features of CRMP-5 PON including bilateral optic disc edema and vitreous cells. However, she was negative for anti-CRMP-5 including a negative Western blot on two occasions, but positive for Purkinje Cell Antibody (PCA)-2. Although paraneoplastic antibodies are more predictive of an underlying cancer than a specific syndrome, previously PON has not been associated with PCA-2. Based on this observation, we recommend that the workup should include PCA-2 antibodies in patients who present with bilateral optic neuropathy and vitreous cells.