Mulder fights to prove that a discovery frozen in the mountains of Canada is an irrefutable evidence of alien life, but his quest for the truth only leads to more lies and an unthinkable conclusion.

The Cigarette-Smoking Man helps Mulder to obtain Scully's cure and also lets him see his real sister who doesn't turn out to be as happy to see Mulder as he would've liked. In return for this, the Cigarette-Smoking Man asks that Mulder quit the FBI and work for him in the Syndicate where he could have power and respect which Mulder turns down, deciding to stay on the side of justice. While Scully's cure appears to have worked, the Cigarette-Smoking Man faces his own enemies and disappears, presumed dead.

On her Christmas vacation with her brother's family, Scully receives a mysterious phone call from a familiar voice who says, "She needs your help. Go to her." The phone call leads Scully to a murder case where the victim's 3-year-old adopted daughter bears an uncanny likeness to her sister, Melissa, at that age. The emotional roller coaster that follows has Scully believing that her sister had a baby during a period when she traveled the country and she tries to adopt the child, knowing that caring for the little girl would change her life.

DNA testing on Emily reveals that she is actually Scully's daughter and Mulder comes to assist her and to find out where and how the girl was born while Scully tries to help Emily with her own serious illness, a rare form of anemia.