Peter heads over to the shelter to help out Aunt May. While he's there, the junkie known as Freak steals the donation box. Peter says he'll go after him and then changes into Spider-Man. He gets Freak cornered on a rooftop but the donation box falls. When Spider-Man jumps down to try to gather the money before the crowd grabs it all, a couple of police officers show up. He leaves the money and takes off.
Freak also managed to take off by pulling himself out of his clothes that were webbed to some pipes. Trying to find his connection's meth lab, he falls through a laboratory's skylight. He figures this is his lucky day when he finds several needles, not seeing the sign that says, "BIOHAZARD. Property of Curt Connors. BHK Stem Cell Project." He injects the stem cells, believing them to be drugs.
Later, Freak is in an alley massively throwing up. Cursing Spider-Man, he is enveloped in his vomit. In the morning at the alley, a strange cocoon is found by a waste management worker, and when he touches it, it burns his fingers. Soon the police and Carlie are there trying to control the crowd and figure out what it is. In Connors' lab, he finds the mess and wonders what happened to his work.
Freak breaks out of the cocoon, surrounded by police officers with Spider-Man looking down. Freak starts moving and an officer with an itchy trigger finger shoots him in the head when he doesn't stop. The shot sends him down into a service tunnel into the sewers. The officers think the problem is over but Freak forms another chrysalis to recover.
After a little while, Freak wakes up. He has changed again. He now has claws and webbed hands. His senses have increased and he continues to blame Spider-Man. Freak makes his way out of the sewer tunnels. Still hungry, he kills a hot dog vendor and notices the torn pants of Spider-Man. Grabbing it, he realizes that he can now follow his scent.
Freak ends up following the scent of Spider-Man to Randall Crowne's campaign event where he just goes berserk and causes all sorts of mayhem down at the event. Civilians start running around insanely trying to escape Freak while he calls out Spider-Man who he smells somewhere in the audience. Peter quickly changes into his Spider-Man attire and swings in to stop Freak. During that time, the police shoot at Freak to discover that his evolution made him impervious to bullets, a factor easily visible when Freak exclaims "HA! IT TICKLES!".
Parker swings in and has a satellite dish thrown at him by his newest foe. Freak lashes out and tries to hit Spider-Man but to no avail and picks up a statue and launches it at Crowne after Crowne barks orders at the immensely disfigured being.
Spider-Man goes just in time to save Freak but is ignored when Freak smells a crack house nearby and rushes off to get the drugs. Freak crawls on the side of the crack house and enters it, his claws open up and he kills the two chemists/makers. He begins to take all the drugs until Spider-Man interrupts him again and the two engage in battle again. Freak gets into a punching bout with Parker until he catches him and prepares to kill him, but before he kills Spider-Man, Spider-Man destroys the crack in the back and sets the entire place on fire. Freak, infuriated by the wall-crawler is caught unaware and Spider-Man escapes Freak's grasp. He battles with Freak again until Freak winds up going into the fire and 'dies'.
Dr. Connors finds out that his stem cell research was stolen by Freak, and alerts Spider-man. Connors tells him that the only way to take out Freak is to cover him in Quick Lime in order to send him into a permanent cocooned stasis. But, Freak is nowhere to be found but, thanks to the cold weather that falls upon New York, Dr. Connors tells Spider-man that it should take some time before Freak hatches from his cocoon this time, due to the reptile DNA in Freak's blood.
Connors finds Freak's chrysalis in a junkyard and passes the information onto Spider-man, telling him that he is bringing the quick lime to the junkyard.
Spider-man rushes to the junkyard after a close call with Menace, and finds that Freak has broken out of his chrysalis and is on the war path, stronger than ever. They tussle for a bit, and Spider-man finally takes him down when he tells Freak that newly-arrived Connors' Quick Lime is actually a batch of drugs. Freak falls for the ruse and breaks open the Quick Lime, inhaling the chemical and promptly falling into unconsciousness.
Last we see of Freak is a giant pupa being wheeled into a deep freeze owned by Oscorp. The Freak is being held in one of Oscorp's labs and is a test subject for various experiments. The Freak is restrained with various tubes sticking out of his body. Norman Osborn and his scientist are discovering how his body removes a weakness every time they kill him in various ways. The Freak wanted drugs for the pain but his body removed the pleasure center of his brain and cured him of his addiction. Osborn decided to inject a new foreign substance into his body to see how he reacted to it. The Freak's body detected the substance and created a biological counter measure. His body began to produce a poison, a super venom that Osborn planned to use for a later date.
After Anti-Venom, Venom, Spider-Man, Norman, Harry, and the Thunderbolts, along with several test subjects escape the crumbling facility, two scientists tell Norman that Freak died in the rubble. Norman reminds them that Freak cannot die.
Freak has the power to evolve every time he is killed by something. He nearly got killed by bullet-shots and fire so now he is evolved to be fire-proof and bullet-proof. He also has superstrength, a healing factor and enchanted smell.