Scream: The Mystery of Ghostface takes place after Scream: The Legend of Ghostface. Fifi is now in the hospital, Melinda and Hayley must find out about Ghostface.
- Emma Roberts as Melinda Roberts
- Georgie Henley as Hayley McDonald
- KeKe Palmer as Sheronda Geords
- Matt Shivley as Kyle Romero
- Miranda Cosgrove as Tamika Lawrence
- Victoria Justice as Sara James
- Dakota Fanning as Tami Jones
- Robbie Amnell as Tyler Fox
- Shanica Knowles as Brandi Cowlin
- Lucas Gabreel as Jamie Hensley
- Leon Thomas III as Tyrone Jackson
- Matthew Lillard as Det Sam Macher
- Jesse Eisenberg-Paul Willson
Det. Sam Macher
Sara James-She was jealous of Melinda's popularity and wanted to frame her for the murders. She wanted everyone to think Melinda was psycho just like her twin sister Jill.
Kyle Romero-Was a film geek like Charlie Walker,he filmed the murders.He only was took part in the first murder.
Jamie Hensley-Sara and Kyle
Tami Jones- Sara
This was the first movie in which Melinda faced some hostlity when she was the main suspect in the murders, there were people telling her that she was just like her twin sister a sick psycho and that she should kill herself. Melinda also recieved a letter from Professor McKenzie saying there is only one to end the curse of Ghostface.
Melinda thought about leaving Woodsboro but Sam Macher convinced her to stay because this was her home and that she should ignore the ignorant people they were always going to think whatever they wanted he went through the same thing when he came back to Woodsboro because of Stu.He said overtime they will come to like and trust you. At the end of the movie Hayley in hospital after she was shot in the stomach by Sara and Melinda has a nightmare about Jill.She wakes up and we see Melinda open up one of Jill's closets and she finds a Ghostface costume hidden there,She takes it out looks at it and smiles like Jill.