After three more wins in Puerto Rico, Santos had a fight in the Dominican Republic, where he beat Mario Ramos by a knockout in the eighth round, on April 2, 1979.
After beating Kid Flash by a third-round knockout on December 1 of that year in St. Thomas, United States Virgin Islands, Santos moved temporarily to Italy, seeking for attention from boxing executives as well as more celebrity than he had in Puerto Rico.
One curious fight happened on December 20 of 1980 in Turin: Santos was credited with beating Alfonso Hayman, a fringe contender of the era, in the first round.
Carlos Santos made his United States debut on May 23, 1981, day in which Wilfred Benítez became the first Hispanic to be a three division world champion in history, when he knocked Raul Aguirre out in the fifth round as part of the Benitez-Hope fight's undercard.
On November 14 of '81, he and Benitez made history by staging the first world championship bout between two Puerto Ricans, when they boxed in Las Vegas, Nevada.
Benitez defeated Santos by a fifteen-round unanimous decision, retaining the WBC world Jr. Middleweight title in an HBO Boxing-televised bout.
Santos, giving Epps more than 40 pounds and a considerable difference in height advantage, won the fight by a first-round knockout.
On his next fight, Santos faced former world Welterweight champion Donald Curry for the USBA's regional Jr. Middleweight title at the Caesars Palace on the Las Vegas Strip.