Tsuna is a hapless youth with low test scores and lower self esteem. His mother hires a tutor to help Tsuna out, but it comes as a surprise to the both of them when the tutor is a baby named Reborn, claiming to be from the Mafia. Reborn informs Tsuna that he's the next heir to the Vongola family mafia family and tries to help Tsuna reach the goal. Reborn possesses the Dying Will bullet, which kills a person and brings them back to life to fulfill the last regret they had, and even works to get Tsuna some henchmen to make him a true mafia boss-in-training.

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Tsuna works very hard to become the 10th Vongola Boss. He is part of the 7 Guardians of the Vongola, he is to be protected by the other 6. In the 7 Guardians, there are 7 elements, (Sky) Tsuna, (Storm) Hayato, (Rain) Yamamoto, (Thunder) Lambo, (Sun) Ryohei, (Mist) Mukuro/Chrome and (Cloud) Hibari.

These 7 Guardians go through a lot of dangerous enemies like Varia, consisting of another 7 enemies which tried to take the Vongola rings, Xanxus, Squalo, Marmon, Mosca (with the 9th inside), Levi, Belphegor and Lussuria. After that, Reborn is sent 10 years to the future, supposingly to come back in 5 minutes, but he didn't, so Tsuna and all the other guardians except for Ryohei and Hibari search for him. They find out that in 10 years, a man called Irie Shouichi has helped the Millifiore family destroy the Vongola family and they succeeded. Tsuna, desperate to go back to the past, attacks Irie Shouichis base at Japan.