NOTE: This spoiler was submitted by Jeremy

Greg Gaines (Thomas Mann) has a story to tell, but he's not quite sure how to start it off. He tries using a stock quote like "It was the best of times, it was the worst of times", and then ponders what the best and worst of times would be, alluding it to a man eating a lot of good food while a girl plays the harp near him. Greg then lets us know that this story of his involves him making a film that literally killed someone.

It starts with Greg entering his senior year of high school. For years, Greg has managed to stay on good terms with every social clique at school without ever actually being friends with anybody. He will bump fists with stoners, nod heads with jocks, and make jokes with the theater geeks, yet he never actually bothered to get to know these people. He eats lunch in the office of his favorite teacher Mr. McCarthy (Jon Bernthal) with his "co-worker" Earl Jackson (RJ Cyler). Earl is the closest thing Greg has had to a friend since he was a kid, but he refers to him as a co-worker since they get together and make intentionally bad remakes of their favorite movies (ie, "A Sockwork Orange" and "2:48 PM Cowboy").

When Greg gets home, his parents (Nick Offerman and Connie Britton) inform Greg of some bad news. His old childhood friend Rachel Kushner (Olivia Cooke) has been diagnosed with leukemia. Greg feels awful since he passed Rachel at school after hearing her friends ask her about a test she took, to which he replied with a joke, unaware of what kind of test she was talking about. Mrs. Gaines makes Greg call Rachel to hang out with her. He does, but Rachel isn't in the mood to hang out. His mom then forces Greg to go to Rachel's house and personally hang out with her anyway.

Greg goes to Rachel's home where her mother Denise (Molly Shannon) is coping with her daughter's illness with wine. Reluctantly, Rachel agrees to hang out with Greg in her room. They have a conversation about the different types of pillows she has in her room, making jokes about masturbating into them and such. At another point, he does a thing where he tries to get Rachel to pretend she's dying after hearing things that annoy her (like someone telling her that the cancer is part of "God's plan"). This causes Greg to imagine Hugh Jackman's voice (from an "X-Men" poster in Rachel's room) chastising him for doing this. Greg realizes his error, but Rachel finds him endearing. Greg then narrates how if this were a romantic story, he and Rachel would lock eyes and start making out...but this is not a romantic story.

Over the next few weeks, Greg spends more and more time with Rachel, even introducing her to Earl. Earl hits it off with Rachel better than Greg, even telling her that he does consider himself and Greg to be friends, but he refuses to use the word because he's awkward and doesn't want to build relationships.

At school, Rachel invites Greg to sit with her and her friends Anna (Natalie Marchelletta) and Naomi (Chelsea Zhang). Also joining them is Greg's crush, Madison (Katherine C. Hughes), whom Greg refers to as a moose that stomps on unsuspecting chipmunks (like himself), so we always see a stop-motion moose stomping on a chipmunk whenever she appears. Rachel notes a pillow that Madison has, asking Greg his thoughts on it. He makes a weird masturbation joke to the disgust of the other girls. Trying to save himself, he makes a comment on the school's weird goth kid Scott Mayhew (Matt Bennett), which Scott hears. Greg flees the cafeteria and goes to Mr. McCarthy's office to find Earl already having lunch there. Earl asks Mr. McCarthy if he can have some of the soup that he brings, but McCarthy can't share his food with students. When he leaves the office, Greg and Earl have some soup, along with some cookies Earl got from the school's resident drug dealer/wannabe rapper Ill Phil (Masam Holden). Afterwards, Greg and Earl get high, thinking that there was something in McCarthy's soup. Later, Scott tells McCarthy in class about Greg thinking his soup had drugs in it, as retaliation for Greg's comment to him. Greg admits that he took some soup but then realizes that he got high off of Phil's cookies. Phil hears that Greg snitched on him, and now Greg has made two enemies in one day.

Weeks later, Rachel has undergone chemotherapy, having to shave her head. She cries because she thinks she's ugly and that people only tell her she's pretty to be polite. To make her feel better, Greg and Earl show Rachel some of their movies, which she finds amusing. When they're shooting a new one near Earl's home, Madison finds Greg and suggests that he and Earl make a film just for Rachel. The guys go ahead and start by interviewing Denise, who shares wine with them. They interview other students while Greg gathers stop-motion clips.

Greg finds Rachel in the library watching one of his movies. She tells him he ought to go ahead and apply for college. He reluctantly goes ahead and applies to Pittsburgh State, which he is later accepted to. As he hangs around Rachel, Greg assures us (more than once) that Rachel survives the end of the story.

Greg is in Rachel's room one day and he asks her to go to prom with him. She declines and adds that she's quitting chemo because it's only making her feel worse. She starts to joke that he can go ahead and take one of her pillows, but it only upsets Greg that she's trying to give up. Rachel hits back that he is only hanging out with her and doing things for her out of obligation (his mom told him to hang out with her, she and Earl told him to go to college, and Madison told him to make the movie) and not because he actually cares about her. Greg leaves pissed off and goes to find Earl, angry with him for telling Rachel about the movie when it was supposed to be a surprise. Earl argues with Greg because he (Greg) is being selfish and treats Rachel like a burden when she is the only other person in school that cares about Greg. Greg pushes Earl into hitting him, and he obliges Greg with a fist to the gut.

Later on, Greg goes home to find a flash drive in his room with a note from Earl saying "I'm out". The file contains a video of Earl's testimony to Rachel. Greg's grades have begun to decline as a result of his time spent with Rachel, and his acceptance to college is rescinded, leaving him with little options post-high school. Meanwhile, Rachel is sent to the hospital as her disease worsens.

On the day of prom, Madison tries to talk to Greg, but he coldly rejects her for always putting her hand on his arm affectionately. He gets up to leave when he's confronted by Phil, still mad at him for ratting him out. He and Greg start fighting awkwardly until Earl intervenes and punches Phil repeatedly. The teachers break it up and kick Phil out. Madison then invites Greg to go to prom with her. He accepts.

That night, Greg gets his tuxedo and rides a limo, not to Madison's house, but to the hospital to visit Rachel. He brings her his finished copy of the movie and plays it using his iPhone and a small projector. It features clips of Greg, Earl, Denise, and Rachel, along with the stop-motion elements that Greg added. Rachel is moved to tears, but then she starts choking. Greg calls in Denise and a nurse as Rachel starts to go still with her eyes wide open. Greg leaves the room and then tells us that Rachel slipped into a coma and died ten hours later. He apologizes for saying that she survived, because he thought she would.

Greg attends Rachel's Shiva, along with his mother and Madison. He finds Earl and reconciles with him. Denise gives Greg the college study book that he shared with Rachel. In it is a note from her that she wrote to him before her death, saying that she wrote to the college to explain that his failing grades were a result of the time spent with her. She also leaves one last joke for him to take one of her pillows, but NOT for masturbating. He then sees two arrows pointing to the middle of the book, where he finds the middle pages cut out to form a little model of Greg, Rachel, and Earl from a time they went to get ice cream. He then sees other drawings and carvings in her room. As Greg leaves, we hear Rachel's voice reading the letter she wrote to the college, telling them to give Greg another chance and that nobody ever made her smile more than he could.

In the end, Greg finishes his story, which was based on his friendship with Rachel. He puts it in an envelope to the college, along with a copy of the movie. He leaves it with a note to warn the admissions directors that the last person to watch the movie slipped into a coma and died.

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