Staffilani grew up on a farm in Martinsicuro in central Italy, speaking only the local dialect, and with no books until her older brother brought some back from his school.

She almost returned home, but remained after Paul Sally intervened and loaned her enough money to get by until the issue could be resolved.

[5][2] At Chicago, she studied dispersive partial differential equations with Kenig,[5] earning a master's degree in 1991 and a Ph.D. in 1995.

While at Stanford, she met her husband, Tomasz Mrowka, a mathematics professor at MIT, and after a year and a half found a faculty position closer to him at Brown University.

[7] Staffilani is a frequent collaborator with James Colliander, Markus Keel, Hideo Takaoka, and Terence Tao, forming a group known as the "I-team".