Mueller spoke during a question-and-answer session with reporters at the FBI's Detroit office, months after an expensive search at a southeastern Michigan horse farm turned up nothing.
"We have a long, long memory," Mueller said. "We will continue to follow any lead that comes to our attention."
Hoffa was last seen alive on July 30, 1975. Over the years, theories have suggested Hoffa was buried at Giants Stadium in New Jersey or dumped in a Florida swamp.
The day he disappeared, Hoffa was scheduled to meet a New Jersey Teamsters boss and a Detroit mafia captain, both of whom are now dead, at a restaurant about 20 miles from the Hidden Dreams horse farm that the FBI searched in May.
The two-week excavation at the farm, about 30 miles northwest of Detroit, involved up to 20 agents, 24-hour guards, archaeologists, anthropologists, a demolition crew and cadaver-sniffing dogs, but it yielded nothing more than a water line, a beer can and other trash.
FBI spokeswoman Dawn Clenney said the search cost less than the $250,000 the agency had budgeted for it.
Mueller would not comment on whether the FBI has any new leads in Hoffa's disappearance, but said the agency will always be working on the case.
"As you can see from the undertakings last summer, we are very willing to follow up on any leads where we believe there is some basis," Mueller said.