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The gene for ataxia\u2010telangiectasia mutated (<jats:italic>ATM<\/jats:italic>) is a prototype for this dual mechanism of action, with loss\u2010of\u2010function mutations causing not only selective degeneration of cerebellar neurons but also increased susceptibility to breast cancer and hematologic malignancy. Increased dosage of amyloid precursor protein in Down syndrome (trisomy 21) predisposes to dementia of Alzheimer type and may also contribute to acute leukemia and transient myeloproliferative disorder. The gene <jats:italic>parkin<\/jats:italic>, loss\u2010of\u2010function mutations in which account for about half of cases of early\u2010onset Parkinson disease, has been identified as a candidate tumor suppressor gene by several groups. <jats:italic>Parkin<\/jats:italic> is deleted or downregulated in several tumor types, and its re\u2010expression sensitizes derivative cell lines to inhibitors of cell\u2010cycle progression. The overlap of molecular pathways implicated in cancer and neurodegeneration challenges long\u2010held notions about differentiated cellular states and may open the door to novel therapeutic approaches to both groups of disorders. 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