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, the regional branch of 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 northeast 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 third fatal crash of an Angel Flight plane since June.
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. On June 3, a Georgia toddler was fatally injured when an Angel Flight plane crashed in Iowa City as it was flying her home.
Each Angel Flight regional group operates independently, but they team up on cross regional flights and meet annually to share information and go over best practices, said Christel Gollnick, CEO of Angel Flight Central, based in a Kansas City, Mo.
The groups combine to make about 20,000 trips annually, she said.
The June crash was the first time in Angel Flight's 25 year history that a patient has been killed during a flight, Gollnick said.
"It's been a very, very sad summer," she said. "The entire Angel Flight world is saddened and surprised and shocked that this is happening all at once."
Gollnick said safety protocols for their planes and roughly 7,000 volunteers have not changed and nothing obvious links the three crashes this year. No formal review is planned, she said.
"We're, of course, asking questions," she said. "Is there any commonality? It's just so strange to have this happen after such a long history."
Easton 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 and the tail stuck out from the rest of the debris, which was covered in tarp 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."
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Associated Press reporters Steve LeBlanc and Jay Lindsay in Boston contributed to this story.
