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De Rossi was born Amanda Lee Rogers in Melbourne, Victoria, the daughter of Margaret, a medical receptionist, and Barry Rogers. She was raised in Grovedale, a suburb of Geelong. As a child, she modeled for print and TV commercials. She took the name Portia de Rossi at a young age:

"When I was 15, I changed it legally. In retrospect, I think it was largely due to my struggle about being gay. Everything just didn't fit, and I was trying to find things I could identify myself with, and it started with my name. I picked Portia because I was a Shakespeare fan (Portia is the character in The Merchant of Venice who comes to the rescue of Antonio and Bassanio in their time of need). De Rossi because I was Australian and I thought that an exotic Italian name would somehow suit me more than Amanda Rogers. When you live in Australia, Europe is so far away and so fascinating, so stylish and cultured and sophisticated."

(Note: Portia de Rossi was also the name of the mother of the eminent 16th-century Italian poet, Torquato Tasso.)

A talented student, she studied at Geelong Grammar School and Melbourne Girls Grammar School, then the University of Melbourne Law School, but left before finishing the course to pursue an acting career. She supports Locks of Love, a group that buys wigs for children with medical hair loss. According to cfidarren.com, Portia is a helicopter pilot, trained by her brother.

Her first significant role was playing a young and impressionable model in the Australian 1994 film Sirens. Soon afterwards she moved to Los Angeles and had guest roles on TV shows including Nick Freno: Licensed Teacher before landing a role in the film Scream 2. She attracted international attention when she joined the main cast of the Ally McBeal TV series in 1998 playing lawyer Nelle Porter. She remained with the show until its end in 2002.

In 2001, she starred in Who is Cletis Tout? with Christian Slater. From 2003-2006, de Rossi starred as Lindsay Bluth Funke on Fox Television's critically acclaimed, Emmy-winning series Arrested Development.

From 2007-2008, de Rossi appears in Nip/Tuck's fifth season as Julia McNamara's new girlfriend Olivia Lord. She also portrayed John F. Kennedy, Jr.'s wife, Carolyn Bessette-Kennedy, in a made for TV movie.

De Rossi, who was married for two years to documentary filmmaker Mel Metcalfe, is now openly gay. From 2000 to 2004, de Rossi dated singer Francesca Gregorini, daughter of actress Barbara Bach and stepchild of Ringo Starr. De Rossi dodged media questions about her sexual orientation and the relationship during this period. De Rossi was rarely pictured with Gregorini in public.

In a September 2005 magazine interview with The Advocate, de Rossi said that most of her family and Ally McBealcast mates learned she was gay because of tabloid pictures of de Rossi and Gregorini in 2001. The couple broke up in late 2004 as de Rossi began dating talk show host and comedian Ellen Degeneres. In 2005, de Rossi officially came out and opened up about being gay in interviews with Details and The Advocate.

De Rossi is currently living with Ellen Degeneres in Beverly Hills, California. On May 15, 2008, the Supreme Court of California overturned the ban on same-sex marriage. On that day, at a taping of DeGeneres's talk show that aired the following day, DeGeneres announced she and de Rossi were engaged to be married. After her partner joked that the couple were holding a gift registry at Crate&Barrel, an unknown source decided it would be funny to actually register the couple there. The couple later made it clear that they were not actually registered and the wedding date is now revealed. Ellen Degeneres announced at the Day Time Emmys.

De Rossi was named number 64 in Stuff's 100 Sexiest Women, 31 in Femme Fatales' Sexiest Women of 2003 list, 24 in Maxim's 100 Sexiest Women List in 2004, and in late 2006, the magazine Blender listed her as one of the hottest women of film and TV. In May 2007, she was featured as one of 100 Most Beautiful in People Magazine special edition. TV Guide includes de Rossi and partner, Ellen Degeneres in their Power A-List couples in 2007.