Jim Peters, a spokesman for the Federal Aviation Administration, said the three were on board the single engine Beechcraft Bonanza when it went down in the parking lot at a Hannaford grocery store at about 10:15 a.m. on Tuesday.
The plane was being operated by Angel Flight Northeast, a group of volunteer pilots that helps people who need to travel for medical treatment, but can't afford it.
Amy Camerlin, a spokeswoman for the organization, said a cancer patient and his wife were being flown to Logan International Airport in Boston so the man could be treated at the nearby Dana-Farber Cancer Institute. It crashed in Easton, about 25 miles south of Boston.
"Right now our primary concern is the family," Camerlin said. "Our thoughts and prayers go out to the family."
It's the second fatal crash of an Angel Flight plane in less than a month. On July 17, an Angel Flight plane crashed shortly after takeoff near Tampa, Fla., killing all three on board, including a 49-year-old cancer patient, a 15-year-old boy and the 81-year-old pilot.
In a statement, Angel Flight Northeast said it had safely flown more than 53,000 people to medical care on 30,000 flights.
Deputy Police Chief Allen Krajcik, said he was in his cruiser Tuesday when he spotted the plane flying at a low altitude just before it dropped out of the sky.
"The plane just did a nosedive, straight down to the pavement," he said
The plane's propellor was found about 50 yards from the crash site. Krajcik said it was uncertain whether it fell off or flew there on impact. Federal investigators are expected to arrive at the scene Wednesday.
The bodies were burned beyond recognition, and dental records may be needed to identify the victims, said Easton Fire Chief Thomas Stone.
Peters said the plane, which was built in 1956, took off from Westhampton Beach on Long Island, N.Y., and was carrying the pilot and a Long Island couple. Peters did not identify the victims.
The registered owner of the plane is Janet Keene of Brookfield, Conn., but she was not on board, according to her husband Kenneth Keene, who called the crash "a disaster."
Kenneth Keene said his wife inherited the plane and sometimes hired a pilot so they could use it recreationally, since neither of them could fly it. He said the plane was used by Angel Flight about once a month and he knew about no problems with the aircraft.
The plane crashed about 500 feet across from the Hannaford entrance, near a road leading out of the lot. Firefighters and fire trucks surrounded the wreckage, where charred wings stuck from the rest of the debris, which was covered in white cloth Tuesday afternoon.
Store manager Arthur Dechellis said the plane crashed in an area where people rarely park and no cars were hit.
Patricia Desgrosseilliers, manager Bank of Easton, near the crash site, said she heard a crash, then saw the plane burning.
"The flame was very tall, very high," she said. "There was a lot of smoke, thick black smoke. ... Everybody was pretty much horrified."
Ashmita Kohli, an employee of a Quizno's in the plaza, told CBS station WBZ she saw at least one body at the scene.
"You could hear a plane then a big boom," she said. "It looks like a movie set right now."
Kholi said the plane was engulfed in flames.
Mansfield Airport is located nearby. Officials there had no comment.
The plaza is home to Hannford's, Quizno's, as well as Target and T.J. Maxx department stores.