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May Reilly fell in love and eventually married Ben Parker. After the death of Richard and Mary, May and Ben took in their son Peter raising him. Peter soon grew up with a great interest in science and academics, causing him to be a social outcast. One day he became slightly more confident and stronger while no longer needing glasses. He began disappearing without word. One night, a burglar entered their home and killed Ben. Peter came by later and learned of his uncle's murder, but disappeared soon after. The burglar was confronted by a new superhero named Spider-Man. She became very nurturing and supportive of Peter and has had financial difficulties since the death of her husband. She introduced Peter to Mary Jane Watson, the niece of her friend Anna Watson. May and Anna set the two up on a blind date and the two went to a school dance. Though the two liked each other, they each began dating other people. Later May began to feel faint while cooking dinner, but shook if off the moment Peter arrives. The whilst out one night show she suffered a heart attack at a Broadway show with Anna Watson during the Sinister Six's attack. Peter, who was under the influence of the symbiote suit, wasn't unaware of it until Mary Jane Watson visited to tell him May was in the hospital.

May Parker recovered and went home for Thanksgiving dinner with Peter, her doctor, Gwen Stacy and Captain George Stacy, where May informed the others that she was writing a cookbook and had already received an advance from a publisher. May Parker is revealed to be feeling much after the heart attack though her nephew still worries. May and Dr. Nicholas Bromwell, have also seem to have an liking over each other. Dr. Bromwell described her as his favorite heart patient and even checking her up at her own home.

May Parker does not know that her nephew is Spider-Man and when asked by the Bugle reporter Ned Lee if he is Spider-Man she thought she was being "punked".

Peter's feelings were mixed in between Liz Allan and Gwen Stacy she gave Peter advice that he needed to be honest between both of the girls but before that he must be honest with himself.

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  • May Parker appeared in The Spectacular Spider-Man voiced by Deborah Strang.
  • Like her movie counterpart, she believed Spider-Man was good.

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