At the start of this issue, Spider-Man drops the unconscious body of Martin Blank off at hospital. Despite that he feels bad about simply dropping him off and not doing more, he is more worried about Aunt May, who's missing. Spider-Man's mind flashes back to all the times he's had with Aunt May, from the time Peter got his diploma, to the time Doctor Octopus moved in with her. Despite that Peter tries to convince himself that it's his fault Aunt May left, he knows that Gwen made Aunt May feel guilty in saying that she was too maternal with Peter.
At that point , a car jacking occurs near where Spider-Man is. For a minute Spider-Man is about to stop the thugs, when he realizes that he should be out looking for Aunt May, not fighting crime. The same thing happens a minute later when he notices a man being held hostage, but would rather be searching for Aunt May.
Spider-Man then returns to his apartment, changes to Peter Parker, and goes to the Daily Bugle, in case Robbie has any leads. Upon getting inside, he finds J. Jonah Jameson in a bad mood, since Peter hasn't taken any pictures for him for weeks. As Peter leaves the Daily Bugle, he runs into Anna May Watson and Mary Jane, who tell him are also worried about Aunt May. After Peter shows them the note Aunt May left for him, Anna points out that Aunt May could have been kidnapped and forced to write it.
Peter then changes to Spider-Man, and swings off to find out what he can about Aunt May's disappearance. After grabbing a criminal and questioning him, Spider-Man finds out that there's currently a gang war on, although the thug won't tell him who it's between. After a few more hours of searching, Spider-Man finds three thugs breaking into a building, and stops two of them. However, the third has a power enhancing harness on, which Spider-Man is unexpected for. After taking the harness off the man, Spider-Man is unexpectedly confronted by one of his deadliest enemies: Doctor Octopus.