|Mark and Ann Telesca are killed in their own home with no sign of forced entry and no fingerprints or clues. Sam notices an entry in John's journal that mentions three other murders in the same area: in 1912, 1945 and 1970. Dean and Sam decide to go an investigate further. When they get to the Telesca house, they find that all the furniture has been removed and sent to an auction house to be sold. They follow, suspecting that it was a cursed item in the house that killed all the couples, as there was no other connection between them.
At the auction house they pose as art dealers and meet Daniel Blake and his daughter Sarah. Sam impresses Sarah with his art knowledge and asks for the provenances - the written history of the items. Daniel refuses and they are asked to leave. Dean encourages Sam to ask Sarah out on a date to try and get some more information from her. Reluctantly, Sam agrees and they go out for a meal in a restaurant together, soon discovering that they have a lot in common and get on extremely well. After their date, Sarah happily gives Sam the provenances which reveal that the link between the deaths is a painting from 1910 which the Telesca's bought a month earlier from a charity auction. Sam and Dean break into the auction house and tear the painting from it's frame. Unbeknownst to them, as they watch the painting burn, inside the auction house, it regenerates itself.
Dean tricks Sam into returning to the auction house to get him to talk to Sarah again. While there, Sam notices the painting and panics. He tells Dean what he saw and they decide to look a little deeper into the paintings origin, The family in the painting is the Merchant family, Isaiah (a barber by trade) and Carolyn, their two sons, Benjamin (aged 14), Steven (aged 11) and their adopted daughter Melanie (aged 9). The story is that Isaiah killed his family and then himself. Dean and Sam believe his spirit is trapped in the painting and is killing these people. His body was cremated, so burning the bones isn't possible. They plan to go back and look at the painting again, hoping to find some clues - also giving Sam another chance to talk to Sarah. Dean encourages Sam to go for it with Sarah, but Sam is unsure. They discuss Jessica and Sam begins to think that it may be time to move on.
When they find out that the painting has been sold again, Sam and Dean rush over to the new owners house, along with Sarah. They find the owner, Evelyn, dead with her throat slit. Sarah asks what is happening and Sam decides to tell her the truth about what they do. She has trouble believing at first but finally realizes that they are telling the truth. She insists on going along with them and helping, despite her fear. A clue in the painting leads to the Merchant crypt in the cemetery where they discover the remains of the family, although Isaiah's remains aren't with them.He was buried apart from the family, not cremated as they thought, so they go to salt and burn his remains, hoping that the murders will be over now. They go back to Evelyn's house to collect the painting, but Sam and Sarah are attacked. The murderer was never Isaiah but his adopted daughter. She tries to kill them while Dean rushes back to the crypt. Despite having been cremated, part of the child still exists - her hair was used for the hair in her doll. Sam and Sarah fight for their lives as Dean recovers the doll and burns it, destroying the spirit of the child. As usual, Dean and Sam don't stay for long, but Sam does finally give in and kisses Sarah before they go. He has finally chosen to move on.