Origin of Homunculi
SPOILER!
2003 vs manga / Brotherhood
2003: Homunculi are tied to failed human transmutation. Dante later stabilizes and manipulates them with Red Stones, and their relationships to the humans they resemble become central to the story.
Manga / Brotherhood: Homunculi have a different origin tied to Father and the seven sins he separates from himself.
Why it matters
This is not a cosmetic rewrite. The 2003 origin turns Homunculi into living consequences of grief, which changes Sloth, Wrath, Lust and the meaning of human transmutation across the entire series.
Alphonse's State Exam
2003 vs manga / Brotherhood
2003: Alphonse prepares for the State Alchemist examination alongside Edward and completes the written portion. Mustang forces him to withdraw before the later stages because exposing the empty armor would reveal the brothers' secret.
Manga / Brotherhood: Alphonse does not take the State exam.
Why it matters
The 2003 version uses the exam to underline how differently the brothers can participate in ordinary society. Ed can let the State inspect him. Al literally cannot.
Shou Tucker's Fate
SPOILER!
2003 vs manga / Brotherhood
2003: Tucker survives his initial scandal, is transformed into a chimera and returns through the Laboratory 5 material still trying to recreate Nina.
Manga / Brotherhood: Scar kills Tucker shortly after the Nina chimera is discovered.
Why it matters
Keeping Tucker alive gives 2003 a recurring image of an alchemist who refuses to accept that his experiment is over. He becomes a grotesque warning about what Ed's own refusal to let go could become.
The Final Conspiracy
SPOILER!
2003 vs manga / Brotherhood
2003: Dante is the hidden architect behind the Homunculi and the repeated search for Philosopher's Stones. Her goal is continued survival through transferring her soul into new bodies.
Manga / Brotherhood: the central conspiracy belongs to Father, a completely different character with a different origin, plan and relationship to the Homunculi.
Why it matters
Once Dante becomes the answer, 2003 stops merely remixing manga events and commits to a different explanation for why so much suffering around the Stone keeps repeating.
What Lies Beyond the Gate
SPOILER!
2003 vs manga / Brotherhood
2003: the Gate ultimately connects Amestris to another world resembling early twentieth-century Earth, and Edward's ending depends on crossing that boundary.
Manga / Brotherhood: the Gate and Truth operate under a different cosmology and do not turn the ending into a parallel-world separation.
Why it matters
The two adaptations do not simply reach different final villains. They eventually disagree about the shape of the universe the brothers live in.