The original sign from Sears Crossing, where the Great Train Robbery began, is selling at Mullock's Auctions on March 18.
It was by the 100 x 17cm metal and wood British Railways sign in Buckinghamshire, UK, that driver Jack Mills brought the Glasgow to London mail train to a halt at an unexpected red signal at 3am on August 8, 1963.
The robbers, lying in wait for the train, attacked both Mills and co-driver David Whitoy, before driving the train half a mile to Bridego Bridge.
There they unloaded £2.6m-worth in money - around £46m ($76.5m) today - before driving to a nearby farmhouse to lie low.
The subsequent manhunt, prison escapes, and the fact that less than £400,000 was ever recovered, have all added to the public's fascination with the robbery.
It helps explain why the piece has a £10,000 ($16,632) high estimate.
Mullock's Richard Westwood-Brookes comments: "With the vast majority of the original trappings of the crime now housed in the official Police Museum and in various institutions around the world, this is possibly the only remaining iconic item available from what has gone down in history as one of the most notorious and audacious crimes of all time."
Its strong provenance adds to its value. The sign comes directly from the family of Leslie Bowler, British Railways' inspector of signals and inspector of movements when the Sears Crossing signal box was decommissioned shortly after the robbery.
In January, Mullock's sold a wanted poster for the train robbers for £4,500 ($7,480), suggesting the estimate on the present lot could be a conservative one.
The auction also features Adolf Hitler's personal directory of SS members. It has a £2,000 ($3,335) valuation.
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