Paraneoplastic neurological syndromes (PNS) can be defined as remote effects of cancer that are not caused by the tumor and its metastasis or by infection, ischemia or metabolic disruptions. In most patients, the neurological disorder develops before the cancer becomes clinically overt and the patient is referred to the neurologist who has the charge of identifying a neurological disorder as paraneoplastic. They are usually severely disabling. PNS are rare and are seen in less than 1% of patients with cancer. PNS depend on an autoimmune process triggered by cancer and directed to antigens common to both the cancer and the nervous system designated as onconeural antigens. Because of their high specificity (>90%), the best way to diagnose neurological disorders as paraneoplastic is to identify one of the well-characterized onconeural antibodies in the patient's serum. In addition, as these antibodies are associated with a restricted range of cancer, they permit orientating the search of the underlying tumor at a stage where it is frequently not clinically overt. This is a critical point, as today the best way to stabilize PNS is probably to treat the cancer as soon as possible. Unfortunately, about one-third of the patients do not have detectable antibodies and 5–10% have an atypical antibody that is not well characterized.