In a statement Sunday, Letta denounced Roberto Calderoli's words as "unacceptable" and "beyond every limit."
Calderoli, the Senate's vice president and a leader of the anti-immigrant Northern League party, made denigrating remarks about Immigration Minister Cecile Kyenge while he was speaking at a party rally Saturday in northern Italy, the populist movement's power base.
"When I see images of Kyenge I cannot help think, even if I don't say that she is one, of a resemblance to an orangutan," the Corriere della Sera newspaper quoted Calderoli as saying.
Kyenge is a Congolese-born doctor who became Italy's first black minister when Letta's Cabinet was sworn in in April. Reactions to her appointment have added to political tensions in Italy this summer, and Letta's coalition government, which faces economic and other pressures, is extremely fragile.
Calderoli told the rally that Kyenge has done well to become a minister, but "perhaps she should do it in her own country." He further was quoted as saying she "makes so many clandestine migrants who come here dream" that they will find "America" in Italy.
The Northern League isn't in the government but has long been the closest political ally of former Premier Silvio Berlusconi's center-right party, which is Letta's main partner in the coalition government. Calderoli's remarks sparked calls for him to resign, including from one of Kyenge's fellow ministers, Gianpiero D'Alia.
D'Alia, a centrist who serves as Letta's public administration minister, told Sky TG24 that Calderoli's comments evoked the kind of racism of the Ku Klux Klan, the U.S.-based white supremacist movement.
Italian media quoted Kyenge as saying she had nothing to say to Calderoli.
Last month, Kyenge, who has lived in Italy since 1983, received death threats before she visited the northern region that is Calderoli's party base. The xenophobic Northern League expelled a local politician after she suggested on Facebook that someone should rape Kyenge so she "can understand what victims of atrocious crimes feel." The League's leaders blame immigrants for violent crime in Italy.
Kyenge has in the past said that such racism is really directed at all Italians, not just her.
Immigration is a relatively new phenomenon in Italy, where past centuries saw many of its own citizens leave in search of work in North and South America and Australia.