The long-running name dispute between Macedonia and Greece dates back to 1991, when Skopje declared independence following the collapse of communist Yugoslavia.
Athens objects to Macedonia's name because it has its own northern province called Macedonia, and fears it may imply territorial ambitions.
The spat has hampered Macedonia's ambitions to join the European Union and the NATO military alliance.
Negotiations to resolve the dispute have made recent progress after Macedonia agreed to change the name of the capital's Alexander the Great airport to Skopje International Airport, in a goodwill gesture to Greece.
The motorway linking Macedonia with Greece was also renamed the Friendship Highway.
"We commend your work with Greece to resolve this issue and I am hopeful it will bear fruit soon," Mattis told Macedonian Deputy Prime Minister and Defense Minister Radmila Sekerinska as she visited the Pentagon.
"We don't wish to see you stopped at NATO's doorstep."
Several possible new names have been floated, with Gorna Makedonija or Upper Macedonia the most frequently mentioned.
Sekerinska thanked Mattis and called for US support to the country's NATO bid.
"We have proven to be a dedicated and reliable partner and we aim to be also such an ally as a member of the alliance," she said.
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