In the previous issue, Spiderman was up against Dr. Doom in an effort to save Flash Thompson from his evil. He managed to get into Doom's ship but doom was prepared for him.
Now, Spiderman is hanging on to life on an electrified plate, completely at Doom's mercy. Doom says that Spiderman has only moments to make his choice. Flash distracts Doom and Spidey takes his only chance to web Doom's armor and make him conductive to electricity. Doom cuts the current to free himself and Spiderman is free. Next, doom uses a variety of other weapons to subdue Spiderman. But Spiderman manages to evade them and webs up Doom's control systems. He manages to capture Doom but discovers that he has been fighting a robot. Doom's face appears on a screen, telling Spiderman that he is defeated.
But suddenly Dr. Doom sees the Fantasticar speeding towards his ship. He weighs his options and makes his getaway. Reed Richards sees that Doom's ship is going to crash into Manhattan. He tells Johnny to prepare a thermal cushion to hold the ship in air, while he tries to free Spiderman. Reed gets inside the ship to find Spiderman and Flash and frees both of them. Johnny drops his cushion and Thing throws a mighty punch that hurls the ship into the river. Spiderman swings off the Fantasticar, saying that he can take care of himself.
Peter walks to class next day, and is disappointed to see Flash bragging about all his recent (exaggerated) adventures with Spiderman. Parker comes into Jameson's office and is askes to submit Spiderman's pictures. Jameson then shows him a video tape, which shows a lizard-like creature threatening innocents in Florida. Peter isn't convinced that it is real.
The next day, Peter sees that the Daily Bugle is challenging Spiderman to fight the Lizard. Spiderman visits Jameson that night and asks him to take Peter Parker to Florida because he will want to embarrass him.
Peter goes to Florida by flight. He is accompanied by Jameson, who reminds Peter that he is here because, Spiderman insisted on bringing him. Peter reads some papers about Dr. Curtis Connors, who is doing Genetic Research in Florida. Peter ditches Jonah at the airport and dresses up as Spiderman to go into the Everglades.
He stops for a second inside the deep jungle, but is immediately attacked by the Lizard. The Lizard can talk and warns him about invading his kingdom. Spiderman tries to grab him, but the Lizard uses his tail to toss him far away. Spiderman manages to stop upon a tree and sees the Connors' house. He comes inside to find Mrs. Connors.
But a sudden child's voice alerts him. He comes out to see the Lizard trying to get away with Billy Connors, the family's only child. Spiderman tries to stop the Lizard but fails. Mrs. Connors insists upon accompanying Spiderman to track down the Lizard. Thay come to an abandoned fortress. Spiderman takes Mrs. Connors atop the fortress, only to find the Lizard and Billy together.
Spiderman tries to attack the Lizard once again, but the Lizard makes his getaway, rebuking Mrs. Connors for betraying him. Spiderman comforts Billy and asks Mrs. Connors about the "betrayal". Mrs. Connors breaks into tears and tells him that Curtis Connors, her husband is the Lizard.
Six months ago, Dr. Curtis Connors had invented a formula which could be used to regenerate lost limbs. He tested it upon his lab iguana and was amazed by the results. But fate had something crueler in store for Connors.
A few weeks later, the Iguana died of a self-sustained injury. Dr. Connors studied its brain, only to find that it was developing towards a mammallian level. Mrs. Connors asked him to postpone the idea of injecting himself with the formula, but it was too late. He had already injected himself, and his right hand had begun to grow. That night for the first time, Connors had strange, alien nightmares, which would continue to re-occur for many days.
The next day, Connors turned into the Lizard and managed to escape his wife and child. He came back normal, but he changed again. Martha Connors was horrified to find him like that, but Curtis Connors ran away from the house. He had already fully changed into the Lizard and there was no turning back.