The latest edition of The Mission Society's "Unfinished" magazine identifies the US as one of the fastest-growing mission fields in the world.
For churches "willing to embrace new thinking", the society says, there are outreach opportunities abound on their own doorstep.
President of the US-based Mission Society, Dick McClain, says: "Acts 1:8 calls us to take the gospel to the ends of the earth while not neglecting 'Jerusalem', our mission field at home.
"Whether you live in Louisville, Kentucky, or Kuala Lumpur, Malaysia, it is incumbent on Christian disciples to identify and then reach out to those who have had the least exposure to the gospel. The least-reached people may very well be your neighbour."
The Mission Society's focus is on reaching the world's least reached, a group typically associated with far off lands.
But The Mission Society says there are also "unprecedented opportunities" for cross-cultural ministries closer to home.
They are urging American Christians to "think cities" and "think universities".
In cities especially, there are fast-growing cultural and ethnic mixtures, as well as people from the least-reached countries who have come to stay temporarily.
At universities, the people from the least reached countries are also part of the all important "next generation".
"Across the boundaries of all these American 'backyards' are some of the world's least-reached," the Mission Society says.
The latest edition of "Unfinished" looks at the work of missionaries in inner-city areas and university campuses, and a church in Atlanta focusing on neighbourhood youths.
Stan Self, senior director of church ministry for The Mission Society, said: "Only when disciples leave the safety of their homes for the least-reached in America's backyard will the Great Commission be fulfilled at home."