In Italy, he was discovered by director Mauro Bolognini and appeared in supporting roles in several drama films during the late 1950s and early 1960s, including Bad Girls Don't Cry (1959) and as Raphael in Carol Reed's The Agony and the Ecstasy (1965).

Throughout the late-1960s and early-1970s, Milian established himself as a dynamic leading actor in a series of Spaghetti Western films, most notably The Big Gundown (1966), Django Kill...

After receiving acclaim for his performance as a psychotic killer in Almost Human (1974), he made appearances in Emergency Squad (1974), The Tough Ones (1976) and The Cynic, the Rat and the Fist (1977).

After returning to the United States in 1985, Milian continued to perform supporting roles in film productions, including JFK (1991), Amistad (1997), Traffic (2000) and The Lost City (2005).

[4] After five years of making what he deemed "intellectual" movies, Milián was unhappy with his contract with producer Franco Cristaldi and thought of going back to the United States.

[3] In addition to his role in Almost Human (1974) and appearances in Emergency Squad (1974), The Tough Ones (1976) and The Cynic, the Rat and the Fist (1977), he also appeared in two film series - Bruno Corbucci's Nico Giraldi series (1976-1984, beginning with The Cop in Blue Jeans) and Umberto Lenzi's Er Monnezza films (1976-1980, beginning with Free Hand for a Tough Cop).

He later turned to comedy, playing the recurrent characters of petty thief Monnezza and Serpico-like police officer Nico Giraldi in a variety of crime-comedy pictures.

Bruno Corbucci, the director of many of these films commented, "At the cinemas as soon as Tomás Milián appeared on the screen, when he made a wisecrack and in the heaviest situations, then it was a pandemonium, it was like being at the stadium.

[9] Milián also appeared in non-genre pictures, such as Bernardo Bertolucci's La Luna, for which he won a Nastro d'Argento for Best supporting Actor, and Michelangelo Antonioni's Identification of a Woman.