In comics, Mattotti won an Eisner Award in 2003 for his Dr Jekyll & Mr Hyde graphic novel.

The story centred on the dreams of a train passenger making it possible for Mattotti to use forms and colors in a way previously unseen in the classic French-Belgian comic world.

He focused more on the inner world of his characters and the total absence of an adventure was also a radical change in the comics universe.

Graphically the album is a highlight in his artistic career: he worked six years on the book, which resembles a gallery of paintings.

Together with his ex-wife Lilia Ambrosi he made this comic about a man who searches his way in the world and who has troubles with relationships.

In Caboto (1992), a comic book he drew as a commission from the Spanish government to commemorate the 500th birthday of Christopher Columbus' discovery of America, he tells the adventures of the explorer Sebastian Cabot.

Stigmates (1998) was a new black and white comic with linear drawings, but darker and more nervous than The Man in the Window.