DePinho was born in the Bronx, N.Y., in 1955. He earned a bachelor’s degree in biological sciences in 1977 from Fordham University, where he graduated summa cum laude as class salutatorian. He received his medical degree with distinction in microbiology and immunology in 1981 from Albert Einstein College of Medicine.

He completed an internship and residency in internal medicine at Columbia-Presbyterian Medical Center, followed by postdoctoral fellowships in the Department of Cell Biology at Einstein and in the Department of Biochemistry and Biophysics at Columbia-Presbyterian.

Prior to joining MD Anderson, DePinho spent 14 years at Dana-Farber Cancer Institute and Harvard Medical School in Boston. Founding director of the Belfer Institute for Applied Cancer Science at Dana-Farber,he served as a professor in the Department of Medicine (genetics) at Harvard and was an American Cancer Society Research Professor. Previously, he held numerous faculty positions during 10 years at Einstein.