In the third season episode "Exodus", Number Three is plagued by disturbing dreams. She visits a human oracle who tells her that Hera, the hybrid child of Karl and Sharon "Athena" Agathon, another copy of the Sharon Valerii model, still lives and that Number Three will play a vital role in the child's destiny. Athena, now a commissioned officer of the Colonial Fleet, later infiltrates the Cylon's New Caprica headquarters. Three tells her that her child is alive, but an unbelieving Athena kneecaps her. After almost all humans have escaped the planet, Three finds Hera accidentally left behind due to the deaths of her adoptive mother and bodyguards, and takes her into the care of the Cylons.
In response to dreams which she believes are messages from God, Number Three begins a series of suicides in an apparent attempt at enlightenment. In the space of time before she awakes in a new body, she experiences a vision of five figures bathed in light, whom she believes are the five unknown humanoid Cylon models.
Three engages in a sexual affair with both Gaius Baltar and Number Six, and claims to love both. However, in the episode "The Eye of Jupiter", she ends the relationship with Number Six, claiming that they have different destinies.
Because D'Anna, with the aid of the other Threes, ignored the consensus decision of the other humanoid Cylons and proceeded with Baltar to the Algae Planet, the other Cylons decided that all members of her model were inherently flawed and suffered from messianic delusions, and would therefore be "boxed" - indefinitely deactivated with their memories permanently downloaded into cold storage. The boxing is carried out by the Brother Cavil model.
Later, when the Cylons split over whether or not to seek out the Final Five Cylon models, which they learn are in the Colonial fleet, the Number Twos, Sixes and Eights call for the Threes to be unboxed to end the deadlock.
In the episode "Faith" the hybrid says "The missing three shall find the five from the home of the thirteenth". Six and Starbuck realize that Three, having previously seen the final five, will be able to recognize the final five from among the presumed humans in the fleet, and that as the five are "from the home of the thirteenth" they are from Earth, the home of the thirteenth tribe of humans. Thus they believe that resurrecting Three will enable the finding of the five and give the fleet a way home to Earth.
Number Three is revived by Cavil in "The Hub". Cavil hopes she will be able to mediate peace between the warring Cylon factions, but she kills him and is taken away by Helo and a Number Eight. Helo takes her to Roslin, where Three tells the President she will only reveal the identities of the Final Five once she's assured of her own safety.