Jessica, played by Hayden Panettiere, is Malcolm and Reese's manipulative neighbor and classmate of North High School. Unlike Cynthia, she has more of a back story and is the only one whom Lois actually likes.
Jessica was introduced as a babysitter to the boys that Hal hired while Lois was gone and has shown how manipulative she was towards them. In later seasons, it's revealed that her father went to jail and she was living with the Wilkerson's house for a while, this revealed her parents are divorced. Despite that, Jessica has also shown that she was a caring friend to Malcolm when she was convinced that Vicki, a beautiful, brainy teen was just using him. She convinced him to break up with Vicki by claiming that she had feelings for him herself, though he was mad at her after realizing that she tricked him once more. She then told him that she was on his side and that their relationship could lead anywhere and then kissed Malcolm. She then said, "Yeah, nothing," revealing it as just another trick. With Stevie's return, she was not present at graduation.
It was also shown that Jessica had dated a tall and muscular Asian guy named Mike, whom Dewey took advantage of so he can torture Reese more and get him beat up.
- Hayden Pannetiere was credited as a guest star in all her appearences despite being famous (this is because she wasn't famous yet to be credited as a special guest star).
- To prepare for her role as Jessica, Hayden had to stop brushing her hair leaving it all messy.
- Despite tricking Malcolm a lot of times, Jessica had genuine feelings for him and went out of her way to help him out. She found out that Vicki despite being a genius underneath, was indeed using Malcolm and lying to him about not wanting to be seen in public in order to maintain her popularity.
- Her favorite pastime is tricking Reese due to his dimwittedness and love of destruction