Confirmed: Lizard for Spider-Man 4
The one armed man is back and he'll be Spidey's nemesis in the follow-up or one of the follow-ups to Spider-Man 3.
From MTV's interview with Marvel supremo Avi Arad:
Arad will then target "Spider-Man 3," due in theaters in May 2007. While insisting that rumors of a simultaneous third and fourth "Spider-Man" movie shoot are simply "not true," Arad did confirm that Dylan Baker will return for the third film — a noteworthy nugget for comic fans who recall that Baker's handicapped character, Dr. Curt Connors, went on to become Spider-Man nemesis the Lizard in the comic books. Although Thomas Haden Church and Topher Grace are set to play the main, as-yet-unnamed villains of the third film, the seeds are apparently being planted for Spidey to also someday take on a superhumanly strong, green-scaled monster.
Source: http://www.mtv.com/shared/movies/interviews/a/arad_avi_062005/