Colombian police confirmed Blanco's death late Monday, with media reports indicating she was shot in the head by gunmen on motorcycles as she left a butcher shop in Medellin, her hometown, The Miami Herald reported.
Ironically, Blanco, dubbed the "Godmother of Cocaine," is credited with inventing the "motorcycle assassin" concept.
Blanco, 69, spent nearly 20 years in jail in the United States for drug trafficking and three murders, including the 1982 killing of a 2-year-old boy in Miami. She was deported in 2004 to Colombia, where she kept a low profile.
"It's surprising to all of us that she had not been killed sooner because she made a lot of enemies," former Miami homicide detective Nelson Andreu, who investigated her, told the Herald. "When you kill so many and hurt so many people like she did, it's only a matter of time before they find you and try to even the score."
She was with a pregnant daughter-in-law, who was uninjured, media reports indicated. El Colombiano said the daughter-in-law told police Blanco wasn't involved in organized crime and was hoping to live on the sales proceeds of properties she owned.
Blanco exemplified the "cocaine cowboy" violence of the 1980s, when drug dealers ambushed rivals in public, the Herald said. She began her criminal career as a thief in Medellin before eventually lording over a drug empire that reportedly shipped 3,400 pounds of cocaine a month to the United States and is considered a pioneer in smuggling drugs from Colombia to the United States.
She ran the organization with her three of her four sons, two of whom were assassinated in Colombia, the Herald said. Three of her husbands also were killed in drug-related violence.
Detectives estimated, conservatively, she was behind about 40 homicides although she was convicted of only three deaths.
In recent years, Blanco was subject of two "Cocaine Cowboys" documentaries made by filmmakers Billy Corben and Alfred Spellman, the Herald said.
"This is classic live-by-the-sword, die-by-the-sword," Corben told the newspaper Monday. "Or in this case, live-by-the-motorcycle-assassin, die-by-the-motorcycle assassin."