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A number of germline syndromes that predispose affected individuals to develop renal cancer have been described, each with unique manifestations, histopathology, and tumor behavior. Patients tend to present with early onset and/or multifocal tumors. Familiarity with these syndromes helps to identify at-risk patients and recommend genetic screening. Early detection is essential to direct appropriate cancer surveillance protocols for patients and other family members and care strategies that preserve lifelong renal function while minimizing risk of death from metastatic cancer.