The story begins with Kazuki Muto, a student in high school, who sacrifices himself to rescue a strange girl from a dangerous creature. He wakes up in his dormitory, believing it was just a dream, but his assumption is proven wrong when a monstrous serpent attacks him and his sister. Tokiko Tsumura, the girl he saved, reveals that the creature is a homunculus and that Kazuki died attempting to save her. Feeling accountable for his death, she revives him with a Kakugane medallion, which acts as his new heart. Tokiko explains that the Kakugane is an alchemical tool that transforms into a unique Buso Renkin, dependent on the user. This tool is the only way to eradicate a homunculus. Kazuki follows her lead and creates his Buso Renkin, the "Sunlight Heart," a massive lance. Together with Tokiko, who wields a Buso Renkin of her own, the "Valkyrie Skirt," an execution scythe, Kazuki embarks on a mission to defeat the homunculi and their leader.