The celebration of Spider-Man's 50th anniversary includes the first ever crossover between the main Marvel Universe (aka "The 616") and the Ultimate Comics universe, where Peter Parker is going to meet Miles Morales, the young man who took up his mantle after a younger version of Peter was killed.
And it looks like the two of them are going to do that classic superhero thing where they misunderstand each other and proceed to fight. Considering the fact that Mysterio is said to be the villain of the piece, they might certainly believe each other to be elaborate illusions.
Spider-Men is also going to "reveal the truth about a major character in the world of Spider-Man." That's always ominous when it comes from writer Brian Michael Bendis, but Ultimate Comics and Ultimate Spider-Man in particular is his wheelhouse.
Check out these preview pages from Spider-Men #2, featuring covers from Jim Cheung, Marcos Martin and Sara Pichelli, who's also doing the interior art.