On a spider web is weaven the words, "A MissedThePart/FandomLover2006/Marvel Entertainment/Marc Webb/Sony Pictures Production". Then, followed, weaved in big text is the text "What If… Spider-Man Gave His Blood to Harry". After that, white text appears, revealing cast member names: ANDREW GARFIELD, DANE DEHAAN, EMMA STONE, JOHN CENA, JONATHAN BANKS, RAINN WILSON, WITH JAMIE FOXX, and finally, "AND ZACHARY QUINTO as QUENTIN BECK / MYSTERIO." Music played. The music of The Amazing Spider-Man 2 (2014) played. In Harry Osborn's apartment, Harry is sleeping when a sound is heard from Spider-Man.

Peter Parker/Spider-Man (hanging above the ceiling): Look up. I think you're looking for me.

Harry Osborn (smiling): I cannot believe my eyes. Spider-Man. He gets up and sits next to him, sirens blaring in the background. Just the man I wanted to see. He pours some whiskey into a glass. You, uh… You talk to Peter?

Spider-Man: Yeah. (After a moment) I want to help you, Mr. Osborn, I really do. I can't give you my blood. Not right now.

Harry (surprised): Excuse me?

Spider-Man: It's too dangerous. If our blood is incompatible, you could die.

Harry (confused): I'm already dying. Your blood can't make me die more.

Spider-Man: But it could do something worse.

Harry: Okay. Well, you're supposed to be a hero. You give people hope. My friend, Peter, was convinced you were a hero and that you inspire hope. Maybe he was wrong. Maybe… (after a pause) you're a fraud.

Spider-Man clearly thinks about this. Harry's words remind him of a flashback from the night Uncle Ben died.

Uncle Ben Parker (to a younger Peter, in the flashback): You're a lot like your father. You really are, Peter. And that's a good thing. But your father lived by a philosophy, a principle, really. He believed if you could do good things for other people, you had a moral obligation to do those things. That's what's at stake here! Not choice! Responsibility.

The flashback ends and Spider-Man sits there, thinking.

Spider-Man (thinking, to himself): With great power comes great responsibility. I have to protect people. I give them hope. Alright, I'll do it. If he's going to die anyway, I might as least try to save him. He's my best friend. God knows if I could save Mom, Dad, Uncle Ben, Captain Stacy, Harry's dad, I would have. Harry is my best friend. Can't believe I'm doing this. But Harry is my best friend. If there's anyone who will understand, he will.

Spider-Man takes off his mask, revealing himself as Peter Parker, and Harry has a look of perplexed shock and disbelief on his face.

Harry: Peter? No, it can't be. It's not possible. It doesn't make sense. How is this possible?

Peter/Spider-Man: It's a long story, Hare.

Harry: So, you're going to help me? But what about all that talk of me possibly dying?

Peter/Spider-Man (smiling, making a Back to the Future reference for the first line of the sentence): I figured what the hell. I might, at least, try to save you. I can't let anybody else die because of this. (Gesturing to the mask, nearly breaking down in tears) After my mom and dad and Uncle Ben… my Uncle Ben told me before he died that with great power, there must also come a great responsibility. You're right, Harry. I'm a beacon of hope. I am a hero. You're going to live, and I am going to give you my blood on one condition: you're the only person who can use my blood. You cannot replicate it. You cannot give it to others. Believe it or not, they're others who want to replicate my blood.

After a moment, Harry thinks, before he nods his head.

Harry: I agree with that. We don't want another Lizard incident, right? That was hell. And we have this electric guy running away. Where do all these guys come from, you know?

Peter/Spider-Man (chuckling nervously): I think his name is Electro. You're definitely right about that, man. I sometimes wonder about that, myself. You're my best friend, and I don't want you to die, man. This thing (gesturing to his mask) is a burden on me and everyone I love. A big secret that I have to keep.

Harry: She knows, doesn't she? That Gwen girl. She knows.

Peter/Spider-Man: Yeah, she knows, man. And she's cool with it. She even helped me cure the city of lizards.

Harry: That's awesome, man! Then, why aren't you guys together?

Peter/Spider-Man: I don't know, man. It's complicated.

Harry (chuckling softly): As I said before, I don't do "complicated". He shakes Peter's hand. I would never do such a thing. You're my best friend. My father may have done that, but I'm not my father.

Peter/Spider-Man: Do you have a syringe anywhere, man?

Harry: Oh, yeah. Somewhere around here. He gets it in a drawer and Peter opens up his sleeve. All right. Well, this is going to hurt, man.

Peter/Spider-Man: Yeah, I know. Do it. Harry injects his blood with the syringe and puts it in himself. He screams from pain at first, but then his veins turn a normal blue. Harry? Are you all right?

Harry: Did it work?

Peter/Spider-Man: It did.

They hug.

Harry: Do you need money? Rent money or something?

Peter/Spider-Man: No. I hate to be a burden.

Harry: Peter, you're my best friend. If you need money, I have a bunch of it. I own a multi-conglomerate billion-dollar company. I can always produce more. There isn't anything you want?

Peter/Spider-Man: Well, there is one thing. Gwen is going to Oxford and I obviously don't have the money for travel expenses. But again, I don't want your money.

Harry: Come on! You deserve to be happy with your girl, man. You helped me, so take it.

Peter/Spider-Man (after a moment, somewhat reluctantly): Okay. Sure, man.

He takes the money. Cut to black. In white text, words appear on the screen, reading "Three Months Later".

The music from earlier in the movie plays as Peter, as Spider-Man, whoops and cheers as he web swings around the city, similar to how he was doing this before going to his high school graduation.

Spider-Man: What do you got for me today, London? This is the best! Whoo-hoo!

Pedestrian: Hey, Spider-Man! London loves you!

Spider-Man: Well, that's a first. New York hated me, and London loves me. It's ironic. Peter's phone rings. Sorry, gotta take this. (After he answers his phone) Yeah?

Gwen Stacy (on the phone): Peter, you should check the news.

Spider-Man: I'm swinging. I really can't right now.

Gwen (sighing): Just check it.

He looks at a news article from his former employer, the Daily Bugle, that reads "SINISTER FIVE LOCATED. NEW CRIMINAL GANG LOOKS FOR MISSING MASKED MENACE SPIDER-MAN." And he sees this on the TV, and he clearly has a horrified expression on his face.

Spider-Man: Oh, shit! Well, I guess I gotta go home. Jesus, Harry, what did you do? I better not have to clean up your mess.

He swings away, leaving London behind, at least for right now. In Midtown Manhattan, The Sinister Five is at a bank vault. The members are Flint Marko/Sandman, Adrian Toomes/Vulture, Dr. Otto Octavius/Doctor Octopus, Max Dillon/Electro, and Quentin Beck/Mysterio. Spider-Man approaches them.

Spider-Man (to the Sinister Five): You really think you can rob a bank in my city? Really? With me around? None of you clowns understand how this works. This is my city.

Max Dillon/Electro (gritting his teeth): Spider-Man. How long have I waited for this.

Spider-Man (gulping): Well, my bacon is cooked.

Cut to black. White text on the screen reads, "To Be Continued?", followed by "Spider-Man Will Return?".

Cast

Peter Parker / Spider-Man — Andrew Garfield

Harry Osborn — Dane DeHaan

Gwen Stacy — Emma Stone (voice only, on the phone)

Flint Marko / Sandman — John Cena

Adrian Toomes / Vulture — Ben Kingsley

Dr. Otto Octavius / Doctor Octopus — Javier Bardem

Max Dillon / Electro — Jamie Foxx

Quentin Beck / Mysterio — Zachary Quinto

London Pedestrian — Tom Holland

Aunt May Parker — Sally Field (archival footage)

Uncle Ben Parker — Martin Sheen (archival footage)