A nationwide manhunt is underway for a fugitive grandma who is accused of murdering two people in Minnesota and Florida — with cops fearing she may kill again.

“She smiles and looks like anyone’s mother or grandmother,” Undersheriff Carmine Marceno, of Lee County, Fla., told NBC News. “And yet, she’s calculated.”

Lois Riess, 56, of Blooming Prairie, Minn., may look sweet and innocent, but authorities say she’s a “stone-cold killer” — wanted for the shooting deaths of her husband, David, and a random stranger named Pamela Hutchinson.

Riess befriended the 59-year-old woman after meeting her at a bar in Fort Myers Beach, Fla., and then shot her dead in an attempt to steal her identity, according to police.

She had already been on the run for several weeks after fatally shooting her husband in Minnesota, cops said.

His body was found on March 23.

Riess is considered “armed and dangerous” by the US Marshals Service — and has been dubbed “Losing Streak Lois” by authorities in Minnesota.

“She is known to have a gambling addiction and often frequents casinos,” federal officials said in a statement. “The fugitive investigation conducted by the U.S. Marshals has Riess’ last known whereabouts in the Corpus Christi, Texas, area in the white Acura TL.”

Police say the vehicle that Riess has been driving belonged to Hutchinson. The two were spotted on surveillance video at a bar on April 5 — just four days before Hutchinson was found shot to death at her condo.

It’s unclear how the pair met, but they can be seen laughing together on the surveillance footage.

“This stone-cold killer was smiling like anyone’s mother or grandmother when she approached our victim,” Marceno said. “She’s an absolute cold-blooded murderer.”

Speaking to WTVR, Hutchinson’s cousin, Daniele Jeffreys, added: “[Riess] probably gave her some sob story. My cousin went out helping the world…She’s just giving to a fault. To her death.”

After allegedly killing Hutchinson, Riess swiped her credit cards and driver’s license, along with her vehicle.

Investigators believe she used the same gun to murder Hutchinson that she used to kill her husband. Riess has been spotted in Iowa, Florida and Louisiana.

Authorities at both the state and federal level have been working together in the hunt for her. She is said to be 5 foot 5, 165 pounds with brown eyes.

“At some point in time (she) will have no resources,” Marceno said. “And she will become more desperate and may kill again.”