Paraneoplastic neurologic syndromes associated with systemic cancer are being increasingly recognized. Although these syndromes are thought to be immunologically mediated treatment with steroids, immunoglobulin and plasmapharesis has been disappointing. Based on our preliminary experience with the treatment of 6 cases of paraneoplastic neurologic syndromes with protein A immunoadsorption, an institutional, open-arm treatment protocol was established. Since our original report we have treated an additional 7 patients with this method. The 13 cases were accrued over a 2 year period and included 10 women and 3 men with an average age of 63. The paraneoplastic syndromes included 6 cases of cerebellar degeneration, 3 cases of opsoclonus/myoclonus, 3 cases of encephalomyelitis and 1 case of Lambert Eaton myasthenic syndrome. Primary cancers included 4 cases of small cell lung cancer, 2 cases of breast cancer, 2 cases of lymphoma and 1 each of acinic cell cancer, cholangiocarcinoma, Merkel cell cancer, pancreatic adenocarcinoma and rectal cancer. Anti-neuronal antibody status, cerebrospinal fluid and neuroimaging studies as well as cancer staging and treatment protocols were reviewed. Neurologic syndromes were clinically separated into component symptoms and signs for assessment of treatment effect. The treatment goal was a total of 6 sessions of protein A immunoadsorption given twice weekly. Twelve of 13 patients completed therapy and one patient developed cutaneous vasculitis during the second session with termination of treatment. Of the remaining patients 3/12 had a complete response of the primary clinical symptom/sign while 6/12 had a partial response for a total response rate of 9/12 (75%). Toxicity was limited to cutaneous vasculitis in 1 patient and an episode of hemisensory changes in another patient. Current treatment of paraneoplastic neurologic syndromes remains unsatisfactory. Despite the small number of patients in this report, protein A immunoadsorption is a promising therapy which deserves further study in a larger population of patients with paraneoplastic syndromes.