Making frequent appearances in the X-Men comics and related spin-off titles, Mr. Sinister has also featured in associated Marvel merchandise including animated television series, toys, trading cards, and video games.

Having felt "tired of just going back to Magneto and the Brotherhood of Evil Mutants and the same old same old" Claremont recalled: Dave Cockrum and I went over ideas, and what we were coming towards was a mysterious young boy—apparently an 11-year-old—at the orphanage where Scott (Cyclops) was raised, who turned out to be the secret master of the place.

[11] Months after his apparent death, backup stories by Claremont published in the reprint series Classic X-Men #41–42 (December 1989) detailed the role Mister Sinister played in Cyclops' early life at an orphanage in Nebraska.

[5] When Apocalypse demands Sinister create a plague that will wipe out much of humanity, leaving only "the strong" alive, the scientist refuses, arguing that cruelty without purpose is ignorance and the enemy of science.

[5] Following the death of Charles Darwin, Sinister travels to America and assumes the identity of obstetrician "Nathan Milbury" (taking the name of his ancestral home), head of the Essex Clinic in New York in the 1890s.

To study how the X-gene may pass on to children in different ways, Sinister arranges for Amanda to marry his former test subject Daniel Summers (who recently became the first of his family to immigrate to America).

As her mind and health deteriorate, she becomes a hospital patient in San Diego for the rest of her life, her treatment provided by Sinister himself, who visits annually in his human guise of Nathan Essex.

[24] Concerned his own physical death may be inevitable, Sinister uses the Cronus Device to implant his own hidden cells of his genetic information into the DNA strands of the Marko, Ryking, Shaw, and Xavier family lines.

Several of his surviving test subjects become deformed or disabled by their own abilities as a result, choosing to hide underground and join a sewer-dwelling mutant community known as the "Morlocks" (taking the name from the subterranean race of the novel The Time Machine).

Becoming aware of Jean's power, Mr. Sinister plans to kill her parents and bring her to the orphanage, only to learn the Greys have already contacted the now adult Charles Xavier for help, due to his background as a leading geneticist and psychological expert in trauma cases.

Hoping to make Cyclops an isolated warrior who can be easily manipulated, Sinister takes on the guise of Nate, another orphan who acts as Scott's overly territorial friend while sometimes bullying him.

[28] As part of his long-term plan, Sinister allows Scott Summers to be adopted by a criminal named Jack Winters who abuses the boy and forces him to help with crimes.

In this reality, Sinister helps Apocalypse rule, adopts both Alex and Scott Summers as his personal soldiers, and recruits Henry McCoy (Dark Beast) as his lab assistant.

Believing Apocalypse will ultimately destroy the Earth in his quest to eliminate the weak, Sinister still works to create a living weapon against him using DNA from Scott Summers and Jean Grey.

[46] Sinister then reveals his true nature and takes over the High Evolutionary's satellite, intending to use it to alter the genetics of people at his discretion, making Earth a giant lab where he could create the ultimate race of superhumans.

Seeing Cyclops' memories of Sinister's obsession with him and learning the scientists treats all of his soldiers and creations like pawns, Xraven flees but takes DNA samples of the X-Men Shadowcat, Colossus, Nightcrawler, and Wolverine.

[58] Though she realizes the secondary and primary mutations caused by such tampering are debilitating to the point of being lethal, Renko works with Bastion, Emma Frost, and Havok to unleash Mothervine on a global scale.

[59] Mothervine bombs containing the catalyst are launched into a dozen major American cities resulting in the emergence of primary mutations in people that didn't possess the X-Gene, as well as the appearance of secondary and tertiary enhancements in mutants.

[69] The auction attendees are evacuated to South Korea's National Intelligence Service Helicarrier as Iron Man, Jessica Jones, Luke Cage, Spider-Man, and X-23 interrogate the seller Declan Fay.

[74] In Marvel's 2019 relaunch of its X-Men franchise, Dawn of X, Sinister finds himself already bored with his new status on Krakoa, and decides to resume his schemes by utilizing a loophole in the Quiet Council rules.

Essex told the two women that Apocalypse did grant him the power to see the future, including major developments in the 20th and 21st centuries such as the escalation of the scale of war and the rise of the machines as the dominant beings on the planet.

After Mystique secretly kills Essex in his cell, covering up her crime in her Holmes form, Destiny finds in a basement level, four human-sized tanks, each one marked with one of the four suits found on playing cards, smashed open and empty.

In this world where Earth's general population became aware of the power and abundance of mutants over a decade earlier than they would have otherwise, Sinister does not bother with manipulating Alex and Scott Summers from the shadows via his orphanage.

Though impressed with Dark Beast's abilities, Sinister is disturbed and at times angry with McCoy's habit of enhancing and altering mutations just for the enjoyment of seeing the results, rather than having a true purpose or benefit for his research.

Unknown to Cyclops, his "father" Sinister is disillusioned with Apocalypse's empire, convinced the mutant conqueror's actions will simply cause the destruction of Earth eventually, leaving no possibility for a master race to live.

Wishing a living weapon he can use against Apocalypse, Sinister clones a powerful mutant from the combined genetic codes of Scott Summers and the X-Man rebel named Jean Grey.

Realizing the boy's raw power could easily burn out his life and body prematurely, Sinister becomes desperate to gain full control of Nathan's mind and abilities to use him as a weapon.

Before Cyclops can lead him to safety, the impulsive teenager immediately unleashes his power and leaves on his own, eventually meeting a group of traveling entertainers called the Outcasts, led by the mutant inventor Forge.

[95] Realizing his creation has fled, Sinister abandons his labs to quickly recapture Nate before he is discovered and killed, knowing Apocalypse will consider his sudden departure a sign of betrayal regardless.

[96] In the Age of Apocalypse 10th anniversary limited series, Sinister collected the seemingly dead Jean Grey after discovering that it was her connection to the Phoenix Force that saved the world from annihilation.