The basic premise behind 042 is that prisoner number 042 is told he is to become a guinea pig in a daring experiment to see if death row inmates can be integrated back into every day life. A microchip is implanted that is set to detonate if 042 becomes angry (and by proxy, is about to kill someone) as a safeguard. He is then made the janitor of a co-ed high school, under constant supervision by a team of scientists led by Dr. Shiina.

What follows is a rollercoaster of events that depicts 042's struggles to fit into a society which has made it clear from the outset that he is not welcome. Along the way, he manages to touch a set of lives who will be forever changed by the encounter, and in turn he will be touched and changed by those who gather around him. In the end, the question is asked: was this experiment a success? Can a convicted serial killer be reformed and re-enter society?