Scully mysteriously appears in a Washington hospital, alive but in a coma, and Mulder must fight to keep her alive in order to find out what happened to her and who did it to her. Meanwhile, Scully fights her own personal battle as she decides whether to stay or go on to the next world.

Scully finds her career with the FBI in jeopardy as Mulder is still missing and the Cigarette Smoking Man is pursuing the stolen files. The Navajo elders find Mulder's body in a cave and perform an ancient ceremony to call the spirit back to the empty vessel.

A.D. Skinner and Scully are at a standoff when Mulder bursts in and discovers that Skinner has the digital tape. Reunited, Mulder and Scully travel to a secret vault inside a mine and find an elaborate filing system of medical records which reveals that Mulder's sister may not have been the first choice for abduction. Meanwhile, Skinner deals with the Cigarette-Smoking Man for their safety.

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.