Around 1.5 million people are being called to vote on the rugged diamond-shaped peninsula, which is inhabited mostly by ethnic Russians.
The choice is between becoming part of Russia or taking more powers but staying in Ukraine -- and a vote for the status quo is not an option.
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The West has said it will not recognise the referendum, while Moscow insists it is an example of self-determination like Kosovo.
Russian troops and pro-Moscow militias took control of the strategic peninsula soon after the Kremlin-backed Ukrainian president Viktor Yanukovych fled Kiev last month after three months of deadly protests against his rule.
Ukrainian military bases in the region -- home to Russia's Black Sea Fleet since the 18th century -- are surrounded but there has been no armed confrontation and it is not clear what will happen to them after the vote.
There have been several attacks on journalists and pro-unity activists condemned by Amnesty International as "extremely worrying".
Washington has dismissed a vote "under the barrel of a gun" and the new government in Ukraine has branded it "illegitimate" and is concerned Moscow is trying to stir up a wider rebellion in Russified parts of eastern Ukraine.
Three activists have been killed in the eastern cities of Donetsk and Kharkiv in the run-up to the Crimea referendum and supporters of Russia have called for similar separatist polls to be held in other Ukrainian regions.
Russian lawmakers have given the go-ahead for President Vladimir Putin to invade Ukraine when he wants, citing the need to defend ethnic Russians against ultra-nationalist radicals.
Ukraine is on full combat alert and on the eve of the vote it accused Russian forces of seizing a village just outside Crimea saying: "Ukraine reserves the right to use all necessary measures to stop the military invasion by Russia".
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