Sackhoff appears as the main character in the Lifetime Original Movie How I Married My High School Crush. She has made guest appearances in Cold Case, ER, Law & Order, and Robot Chicken. Sackhoff provided the voice of a female marine in the video game Halo 3 and is featured in the viral marketing campaign for Resistance 2. In 2011, she provided the voice for Black Cat 2099 in Spider-Man: Edge of Time. She voiced Sarah Essen in the DC Comics animated film, Batman: Year One. She appears in four episodes of the fifth season of the series Nip/Tuck playing a new Doctor, Dr. Theodora Rowe. However, for the sixth season Sackhoff was replaced by Rose McGowan for the role due to scheduling conflicts. Sackhoff headlined NBC's Dick Wolf-produced cop drama Lost and Found as Tessa, "an offbeat female LAPD detective who, after butting heads with the higher-ups, is sent as a punishment to the basement to work on John Doe and Jane Doe cases." The pilot was filmed in January 2009. NBC decided not to pick up the series. In 2009, she appeared as herself in "The Vengeance Formulation" episode of the CBS situation comedy The Big Bang Theory. In the episode, she is fantasized as Howard Wolowitz's dream girl. She appears again in season 4, in the same role. Sackhoff appeared as a series regular in the eighth season of the TV series 24, playing Dana Walsh, a CTU data analyst with a secret. In February 2010, Sackhoff signed on to play the lead in an ABC crime drama pilot, Boston's Finest. ABC decided not to pick up the series.

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