I did theater at Carnegie, and in Pittsburgh and New York.

However San Giacomo first drew international attention in Steven Soderbergh's Sex Lies and Videotape (1989) which also marked her film debut as a credited actor (in the 1988 movie Miles from Home her role as "Sandy" was not credited). San Giacomo discovered acting while attending Morris Knolls High School. She lives in the San Fernando Valley in California.

She most recently played the role of Holly Hunter's childhood best friend on the TNT crime drama series Saving Grace.