Nortwest Orient Airlines flight 2501 was a DC-4 aircraft which was flying between NYC and Seattle, WA in June 1950, carrying 55 passengers and 3 crew members.
Last contact with the aircraft was when it was flying over Lake Michigan at 3,000 ft. She abruptly disappeared from radar and the presumed wreckage was never located. This despite the use of sonar and dragging the bottom of Lake Michigan with trawlers.
Even with modern technology in use (side-scan sonor, etc) the presumed wreckage was never found.