Paraneoplastic syndromes are uncommon manifestations of cancer not directly related to mass effect or to a substance normally produced by the cancerous tissue. They are often classified by the affected organ system and may present before or after the diagnosis of cancer. Neuroendocrine tumors are most likely to cause paraneoplastic syndromes. In patients with no known malignancy, the diagnosis of a well-characterized paraneoplastic syndrome should prompt a cancer work-up, including age-appropriate cancer screening and, if applicable, targeted testing for cancers associated with the specific paraneoplastic syndrome. Not all syndromes resolve even with cure or remission of the underlying cancer.