Santino is an Italian vampire made in the 13th century. Having lost his family to the plague, he was walled up within his home with their corpses, and discovered by a wandering vampire who could not find any remaining living humans in his town. He became the leader of a Roman coven of the Children of Satan and in 1499, led an attack on Marius de Romanus's residence, kidnapping Amadeo (who had recently been made into a vampire by Marius) and the rest of Marius's young pupils. Santino renames Amadeo to Armand, finding the name Amadeo, meaning "Beloved of God" to be against his coven's beliefs. His coven burns Marius's pupils alive and converts the traumatized Armand to the ways of the Children of Satan, eventually sending him away to lead his own coven in Paris. By 1780, Santino has left the Children of Satan, and has fallen in love with and been rejected by Pandora. By the 20th century, he has a companion named Eric, with whom he visits Maharet's home in Sonoma.
In 1985, Santino answers Marius's telepathic cry for help with Pandora, and rescues him from where he is trapped in ice in Alaska following Akasha's reawakening. Santino goes to Maharet's home with Marius and Pandora, and witnesses the death of Akasha. Santino moves with the other vampires to Night Island, and is seen playing chess with Armand at the end of The Queen of the Damned. After Armand is apparently killed in New York following the events of Memnoch the Devil, Santino and Marius visit a coroner's office to retrieve the remains of vampires who have chosen to self immolate.
At the end of Blood and Gold, Santino is brought to Maharet to be judged after Marius acknowledges he still wants justice for what was done to him in Venice, but Maharet declines Marius's request to kill Santino. Displeased with the decision, bitter at Maharet, and vicariously angry on Marius's behalf after hearing his story, the vampire Thorne kills Santino with the Fire Gift.