The holiday season has started but not everyone is in a festive mood. This is Alex's last day in the hospital unless he passes his boards practical exam the next day, thus everyone helps him to review so that he succeeds. However, Izzie is not happy about the others helping him and Meredith has to remind her of the true spirit of the Christmas holiday. Justin is in need of a new heart. One is available but he does not want it because he does not believe Santa gave it to him as his mother said. Cristina and Burke, both handling Justin's case, have opposing views on the matter due to their different stances on religion. Despite a reconciliation with his wife, Derek isn't in a festive mood. George has a simple case of a woman who has a bleeding ulcer, he realizes that the ulcer is caused by her entourage but fails to keep them away, with the consequence that it perforates.

After being humiliated by Mrs. Krabappel's class, Mr. Burns finally decides to buy a new car, so he orders a Lamborgotti Fasterossa. He sends Homer and his family to the factory in Italy to pick the car up. The family takes a tour of Italy in the new car, but an accident with the car and a cheese truck has the family pushing the car into the town of Salsiccia. They find out that only one person in the town speaks English and it happens to be their mayor. The family goes to meet the mayor and they are surprised to see that it is Sideshow Bob, and he is equally surprised to see them. Sideshow Bob tells them how he came to Italy, become mayor and started a family with his wife (Francesca) and son (Gino). He hopes that the Simpsons will keep the secret of his criminal past, but Lisa’s first exposure to drinking wine leads to loose lips, which sinks his ship. Sideshow Bob, being no longer welcome in his new home, swears a vendetta on the Simpson family. The Simpsons go on the run

James and Richard are once again trying to beat Jeremy in another of their now famous races. This time, the race is on to see who will be the first to get from Alba in northern Italy, to the NatWest Tower in London. James and Richard are in a light aircraft piloted by James, while Jeremy has to make do with a Bugatti Veyron. Former F1 and Indycar World Champion Nigel Mansell gets the chance to set a fast lap in the Liana.