In the light of day and in the dead of night, mysterious horrors await in the darkest shadows of every corner. They are unexplainable, inescapable, and undefeatable. Be prepared, or you may become their next victim. Sit back in terror as traumatizing tales of unparalleled terror unfold. Tales, such as that of a cursed jade carving that opens holes all over its victims' bodies; deep nightmares that span decades; an attractive spirit at a misty crossroad that grants cursed advice; and a slug that grows inside a girl's mouth. Tread carefully, for the horrifying supernatural tales of the Itou Junji: Collection are not for the faint of heart.

Ever since Rentarou Aijou found out that he would meet a total of one hundred soulmates in high school, his life has been anything but boring. Now with six girlfriends—each with their own unique quirks—Rentarou has never been happier. The group expands once again when Rentarou meets Kurumi Haraga, a girl with a never-ending appetite; and Mei Meido, the maid of the Hanazono family. As he encounters more of his soulmates, Rentarou has to juggle ways to date them all, since failure results in a grim fate. Fortunately, Rentarou has no shortage of love to give to each of his girlfriends!

First loves are messy. While settling in as a shoujo manga editor at the famous Marukawa Publishing House, Ritsu Onodera is quite troubled. Working under the stern and superb Masamune Takano is hard enough as it is. However, Masamune is not only Ritsu's first love from middle school but he also suddenly declares that he will make Ritsu fall for him again. Unknown to them, another editor in the department, Yoshiyuki Katori, is in a relationship with the popular manga artist Chiaki Yoshino. The carefree Chiaki fails to notice, however, that his high school friend—Yuu Yanase—thinks of him as more than a friend. The stoic but caring Hatori will not surrender his love so easily. Falling in love for the first time when you are 30 is certainly troublesome. Shouta Kisa, yet another editor, is going out with 21-year-old Kou Yukina, an art student. Despite Yukina's assurances, Kisa cannot help but doubt whether someone like himself is truly worthy of his younger, sparkling boyfriend.

In an isolated village, two twins were born, separated by day and night. It is years later, and while the older brother Yuru has become a hunter of animals, his sister Asa has been locked away in a cage, ordered to perform a special duty that prohibits her from meeting more than a few select individuals. On an otherwise inconspicuous day, a group of armed men riding in helicopters, referred to as dragons by the citizens, assaults the village in search of Yuru, killing every adult on sight. When Yuru attempts to meet up with Asa and flee, he finds a dead body instead—on top of that, the person who killed her claims to be Yuru's true twin sister. Before the woman can capture him, Yuru is rescued by a man named Ryuu Dera Tadera, an outsider who frequently visits the village. However, it is not long before the two are cornered. In a last-ditch effort, Dera makes Yuru give a gift to the deity of the village, summoning a pair of daemons whose existence is bound to reveal the truth behind these chaotic events.