Born in Cantanzaro, Italy, Dulbecco obtained his MD from the University of Turin in 1936 and taught there until 1947 when he moved to America. He taught briefly at Indiana before moving to California in 1949, where he served as professor of biology (1952–63) at the California Institute of Technology. Dulbecco then joined the staff of the Salk Institute where, apart from the period 1971–74 at the Imperial Cancer Research Fund in London, he remained, latterly as President Emeritus.

Beginning in 1959 Dulbecco introduced the idea of cell transformation into biology. In this process special cells are mixed in vitro with such tumor-producing viruses as the polyoma and SV40 virus. With some cells a ‘productive infection’ results, where the virus multiplies unchecked in the cell and finally kills its host. However in other cells this unlimited multiplication does not occur and the virus instead induces changes similar to those in cancer cells; that is, the virus alters the cell so that it reproduces without restraint and does not respond to the presence of neighboring cells. A normal cell had in fact been transformed into a ‘cancer cell’ in vitro.

The significance of this work was to provide an experimental set-up where the processes by which a normal cell becomes cancerous can be studied in a relatively simplified form. It was for this work that Dulbecco was awarded the Nobel Prize for physiology or medicine in 1975, sharing it with Howard Temin and David Baltimore.

In March 1986 Dulbecco published a widely read paper in Science, entitled A Turning Point in Science, in which he argued that “if we wish to learn more about cancer, we must now concentrate on the cellular genome.” The paper appeared shortly after various groups of scientists had held a meeting at Sante Fe to discuss sequencing the entire human genome. Dulbecco's timely paper publicized the project, gave it some authority, and linked it with a practical purpose.