It tells the story of William Cole, a pharmaceuticals magnate who, while finalizing a deal in Bulgaria, suffers severe brain damage in an attack by Tatoya, a vengeful gypsy woman. A well-meaning Mad Scientist repairs Cole's brain with tissue from KGB-agent-turned-taxi-driver Yegor, Tatoya's former lover and another one of her victims. Now Cole and his Split Personality Yegor must work together to hunt down the woman who tried to murder them both. Complicating matters is Jackie Cole, William's wife, who attempts to track down Tatoya herself only to die and have her brain transplanted into the body of a robot.
Man with the Screaming Brain provides examples of:
- Aw, Look! They Really Do Love Each Other: The Coles spend the entire first act sniping at each other. When William ends up in a coma, Jackie laments that they never had the chance to rekindle their love for each other. They do.
- B-Movie: And proud of it!
- Flashback Cut: Post-surgery Cole receives flashes of Yegor's memories in this way.
- Hot Gypsy Woman: Tatoya.
- I Want You to Meet an Old Friend of Mine: The movie co-stars frequent Campbell collaborator Ted Raimi as Pavel. Campbell also previously directed Tamara Gorski in two episodes of Hercules: The Legendary Journeys.
- The Igor: Pavel. He does a lot of corpse-collecting.
- Jerkass: William Cole is a straight-up Flavor 2 Eaglelander.
- Mad Scientist: Dr. Ivan Ivanovitch Ivanov.
- Police Are Useless: Even if we accept the movie's premise that Bulgaria is a lawless hellhole, it's still hard to imagine why no one investigated any of the murders even though the newspapers had reported them. Also, Pavel was able to steal the bodies, unexplained and off screen, with no trouble at all.
- Pretty Fly for a White Guy: Pavel, played by Ted Raimi, has adopted the style of urban American youth. Fo' shizzle.
- Psycho Ex-Girlfriend: Tatoya spends much of her time in a bridal shop wearing a wedding dress, and ends up attacking the protagonists because Yegor sold what was to be their wedding ring to Cole.
- Scars Are Forever: Surprisingly — hell, amazingly, considering what Cole's forehead looks like through most of the film — averted. His gigantic, clumsily-stitched scar is completely gone six months after his adventure. And Jackie only sports a little discoloration on her forehead.
- Slapstick: It's directed by Bruce Campbell, the master of physical comedy. And, yes, he does spend some time fighting his own hand.
- Split-Personality Merge: Never quite happens, but the epilogue reveals that Cole and Yegor are now close friends.
- Trauma-Induced Amnesia: After the surgery, Cole doesn't recall who he is until he sees himself in a newspaper.
- We Can Rebuild Him: Jackie Cole is killed by Tatoya, and Dr. Ivanov places her brain in a robot body; she escapes to take revenge.
- Why We Are Bummed Communism Fell: Yegor earnestly believes that the fall of communism is a bad thing for his country. Also, being a KGB agent is a much sweeter gig than driving a cab.