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| Ioan Gruffudd | Reed Richards/Mr. Fantastic |
| Jessica Alba | Susan Storm/Invisible Woman |
| Chris Evans | Johnny Storm/The Human Torch |
| Michael Chiklis | Ben Grimm/The Thing |
| Julian McMahon | Victor Von Doom |
| Kerry Washington | Alicia Masters |
| Andre Braugher | Gen. Hager |
| Laurence Fishburne | Silver Surfer |
| Beau Garrett | Capt. Raye |
| Brian Posehn | Wedding Minister |
| Zach Grenier | Mr. Sherman/Rafke |
| Kenneth Welsh | Dr. Jeff Wagner |
| Doug Jones | Silver Surfer |
| Giuliana DePandi |
Reed, Susan, Johnny and Ben face an intergalactic messenger who has arrived to prepare Earth for its destruction. While the enigmatic being wreaks havoc around the world, the heroic quartet must also contend with the unexpected return of their enemy, Victor Von Doom.
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