It is said that the Virgin Mary, the messenger and the hope of the Roman Catholic Church, will reincarnate as a girl with "cross stigmata." Nagisa Akira bears a cross-shaped mark on her chest, but as far as she is aware, she possesses no holy powers. Rather than being treated like a reborn saint, she wants to be nothing more than a normal schoolgirl.

Akira was orphaned eight years ago and came under the protection of the church, "Bethlehem," in Japan. When her whereabouts become known to the Vatican, they send an elite team from their private army, the Crimson Cross, to act as her bodyguards. Among them is Chrome Takagi, codenamed "Crimson," who is a prodigy extraordinarily capable of dealing with demonic powers.

At the same time that the Vatican takes notice of Akira, she also attracts the Tiamat Financial Group's interest. Supposedly, Tiamat is controlled by demons, particularly nine immensely powerful "Numbers." Tiamat immediately comes after Akira, but their leader, Cyus, seems strangely more fixated on Chrome than on her.