Paraneoplastic manifestations are present in up to 20% of patients with renal cell carcinoma (RCC). There is convincing evidence that RCC tumor cells elaborate proteins that serve as mediators of endocrine (eg, ectopic production of parathyroid hormone-related protein or erythropoietin) as well as nonendocrine paraneoplastic syndromes. A paraneoplastic syndrome may be the initial clinical presentation of RCC in a significant number of patients, and recognition of these syndromes may facilitate early diagnosis. Most paraneoplastic syndromes associated with RCC remit after resection of the primary RCC or treatment of metastatic sites. The natural history of metastatic RCC is extremely variable. A significant proportion of patients may survive several years with slowly progressing metastatic disease. In these patients, the accurate diagnosis and management of paraneoplastic syndromes may be important in palliative management. Except for hypercalcemia, conventional medical therapies are seldom helpful. Other paraneoplastic manifestations of RCC include cachexia, fever, hepatic dysfunction, anemia, and amyloidosis, although our understanding of the underlying pathophysiology remains incomplete.