Lantos, 79, posted the announcement on his congressional Web site.
"Routine medical tests have revealed that I have cancer of the esophagus," he said. "In view of this development and the treatment it will require, I will not seek re-election."
Lantos, a World War II Holocaust survivor and founder of the Congressional Human Rights Caucus, was elected to Congress in 1980. He currently serves as chairman of the House Committee on Foreign Affairs.
Born in Budapest, Hungary, he immigrated to the United States in 1947 as a college student.
"It is only in the United States that a penniless survivor of the Holocaust and a fighter in the anti-Nazi underground could have received an education, raised a family, and had the privilege of serving the last three decades of his life as a Member of Congress," he said. "I will never be able to express fully my profoundly felt gratitude to this great country."
Lantos said he and his wife, Annette, plan to continue working on behalf of "human rights, civil liberties and social justice" after he leaves office.