At La Casa di Sol, an ancient Venezian home of various composers through the ages, a young violinist practices a piece by Paganini and then inexplicably electrocutes her bathing mother with a hair dryer. We then see a female rock band recording in a studio who are told by their manager, Lavinia, that they should find a new song. The drummer, Daniel, travels to a secluded location, where he meets with Mr. Pickett, who sells him an unpublished score by Paganini. Daniel demonstrates the new piece, "Paganini Horror," for Lavinia and the lead singer, Kate, and explains its origins, with all three agreeing to record it. Lavinia suggests they employ famed horror director Mark Singer to film a video and Kate suggests they film at La Casa di Sol, with Lavinia adding that she knows the current homeowner, Sylvia.
On the video shoot for their new song, Sylvia reveals the legend that Paganini himself once resided in the house and murdered his bride, Antonia, there. Meanwhile, Pickett travels to St Mark's Campanile, where he throws the money Daniel has given him off the roof and invokes Paganini's curse.
Rita, the bass player, is confronted in the dressing room by Paganini, who she assumes is Daniel wearing his costume from the video shoot; however, he stabs her to death with a violin. Sylvia and Elena, the guitarist, announce that Rita has vanished; Lavinia suggests she be replaced, while Mark suggests they finish the video using mannequins. While going to collect the mannequins, Daniel sees Rita and is summoned by her to another room, where he is murdered by Paganini.
Sylvia finds Daniel's ring atop a human-shaped pile of ash. They decide Daniel has played a joke on them when the ground opens beneath Kate's feet and she falls. As Mark tries to help her out of the hole, he is electrocuted, dropping Kate into the hole. Mark and Elena are driven from the house by deafening sounds, but when they try to escape, their car hits an invisible barrier, ejecting them from the car and engulfing it in flames. Lavinia finds a tunnel in the hole and descends to try and locate Kate. Elena and Sylvia hear Lavinia scream, but Elena believes the scream came from upstairs, which leads Sylvia to investigate, leaving Elena to fend for herself.
Sylvia, hearing ghostly violin music, ascends the stairs, and as she reaches the top she sees Daniel outside in the courtyard. After quickly descending the stairs and exiting the house to greet him, only to find he has vanished, she discovers a bewildered Kate in the empty courtyard pool and the two agree to find the others and escape.
Lavinia finally emerges from the hole and reunites with the others, realizing Elena has now gone missing. Following a trail of blood, they ascend the staircase and find a dying Elena, covered in blood and gasping for air. Lavinia recognizes the fungus on Elena and says it was found on logs during the 18th century, with the wood being used to make Stradivarius violins. Kate, resolving that the only way to rid the house of the curse is to use Paganini's piece as a weapon, plays the melody on her violin. However, when they attempt to escape the house, they find that the invisible barrier is still in place.
Kate decides the curse could be lifted by playing the piece backwards, but when Kate attempts this, the sheet music electrocutes Lavinia and flies out of her hands, bursting into flames. Lavinia then finds herself trapped behind an invisible wall, which crushes her to death. Paganini emerges, stabbing Sylvia with his violin and sealing the unconscious Kate in an empty double bass case. As he plays his violin, Kate awakens inside the case, which catches on fire. The sun rises and emerges through the open window, killing Paganini and reducing him to a pile of dust in the shape of a treble clef, while incinerating both the sheet music and his violin.
Kate exits the house as Sylvia, thought to be dead, arrives by car and explains that, because Kate never played the piece backwards, Paganini's curse will continue. Pickett emerges from the car as Sylvia explains that she was the one who, as a child, had murdered her mother in the house, and that she was condemned to relive the experience for eternity. Meanwhile, Pickett explains that all visitors to the house have already been condemned to Hell. As a new family arrives, Kate theorizes that she is free to go, but Pickett explains that he hates people who sell their souls for fame and success and stabs her to death.
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