- Vito: "You El Greco, the doctor?"
- El Greco: "No, I'm the fucking painter."
- ―Vito and El Greco in The Buzzsaw.
El Greco studied medicine in London, and originally served as a doctor in the Greek Embassy. He was transferred in 1927 to the office of the U.S. Ambassador in Empire Bay. El Greco was dismissed from the embassy three years later after a dalliance with the Ambassador's wife, and went into private practice. After being handsomely rewarded for saving the lives of a number of gangsters during Empire Bay's Vinci-Moretti War, he began offering his services to the underworld.
He is first seen in the opening scene inspecting immigrants who came from Europe. He is seen again in The Buzzsaw when Henry Tomasino is shot in the leg by Sidney Pen, and finally when Joe Barbaro and Vito Scaletta were kidnapped by the Vinci during Stairway to Heaven, during which he mentions how Antonio Balsamo will never walk again.
- El Greco means "the Greek".
- He has a large home in Highbrook.
- El Greco seems to have a similar role as The Doctor from the first game.
- It was suggested that El Greco's favorite dish is Souvlaki, as mentioned by Joe in The Buzzsaw.
- A running joke is that no one seems to know the difference between him and a painter of the same name.