Two years ago, Ayumu Narumi's older brother Kiyotaka Narumi, a famous detective and pianist, disappears without a trace. Ayumu's only clue as to his brother's whereabouts is the phrase "Blade Children," the only words Ayumu could make out in Kiyotaka's final phone call. Now in high school, Ayumu becomes involved in solving in a series of murders and other incidents, all related to the Blade Children. Together with his school's journalist, Hiyono Yuizaki, and the unwilling assistance of his sister-in-law, Madoka Narumi, Ayumu tries to figure out who the Blade Children are and what are their goals.

The Blade Children are the central mystery of the series, known only as cursed children that few know about and are being pursued by so-called Hunters. They are distinguished by their cat-like eyes (though a few lack this feature) and by missing the seventh right rib bone. As Ayumu investigates them, he meets Blade Children Kousuke Asazuki, Rio Takeuchi, Eyes Rutherford, Ryoko Takamachi, and Kanone Hilbert, and is tested in various ways by them. Those who meet him eventually conclude, some more reluctantly than others, that Ayumu does have what it takes to "save" the Blade Children, as they say Kiyotaka claims.

The anime series, which adapts the story through the sixth volume of the manga, compares the Blade Children to cuckoo birds, having been deposited in human "nests" to be raised, and suggesting that cuckoos go violently crazy toward the end of their lives. The manga continues the story, depicting Ayumu's discoveries about the origin of the Blade Children, their relationship with Kiyotaka, and why his older brother thinks Ayumu might be their savior.

Some thirty years ago, a man called Yaiba Mizushiro was born with one rib missing from his right ribcage. Like Kiyotaka, he excelled at everything he chose to put his mind to. When he turned twenty-three, Yaiba started his own secret society, which swiftly grew powerful enough to manipulate world events. Citing boredom, Yaiba initiated the "Blade Children Project": using in vitro techniques and his DNA, he created eighty children, and had a rib removed from each of them at birth as a mark of their relationship to Yaiba. These Blade Children were cursed in the same way Yaiba was: they would grow up as geniuses in their own right, but one day their blood would awaken murderously and take over their self-will, becoming Avatars of Yaiba. Yaiba's organization split into three parties over the Blade Children Project:

  • The Savers supported Yaiba's goals and desire to create more Blade Children. With Yaiba's death, they sought to protect the fact the future had not been determined yet.
  • The Watchers were neutral, wanting to observe the first batch of Children and gather results first.
  • The Hunters were against Yaiba, and tried multiple times to assassinate him, but repeatedly failed. After Yaiba's death, they worked to eliminate the Blade Children because of their potentially dangerous natures.

When Yaiba was thirty-six, a Japanese man came out of nowhere and easily killed him: Kiyotaka Narumi, Yaiba's counterpart—if Yaiba had been a destroyer, Kiyotaka was a creator. Yaiba had intended to remake the world literally in his own image; with his death, the Blade Children project was halted. Kiyotaka had his hands full trying to stop the Hunters from killing the Blade Children, while trying to check the Savers at the same time.

Just as Kiyotaka and Yaiba were linked, Ayumu eventually meets his own counterpart: Hizumi Mizushiro, Yaiba's younger brother, and the one who will awaken the blood of the remaining Blade Children. As Ayumu comes to know and becomes friends with Hizumi, he comes to accept his own powers are as strong as Kiyotaka's and his role as the savior of the Blade Children, leading to a final confrontation that resolves things once and for all.