The consultative votes are only the beginning of a process which could over time lead to powers being devolved from Rome.
Secessionist sentiment in the two wealthy regions is restricted to fringe groups with little following.
Nonetheless, with both regions expected to vote in favour of the principle of greater autonomy, analysts see the referendums as reflecting the pressures that resulted in Scotland's narrowly-defeated independence vote, Britain's decision to leave the EU and the Catalan crisis.
There is no threshold in Lombardy but low voter participation would weaken the region's hand in any subsequent negotiations with the central government.
European Parliament chief Antonio Tajani today took care to distinguish between Catalan's chaotic independence referendum, deemed illegal by Madrid, and the votes in Italy.
"First of all these two referendums are legitimate, that was not the case in Catalonia," he told the Rome daily Il Messaggero.
He said Europe should "fear" the spread of small nations: "It is not by degrading nationhood that we reinforce Europe.
Lombardy, which includes Milan, and Veneto, which houses Venice, are home to around a quarter of Italy's population and account for 30 per cent of its overall economic output.
With dynamic economies and lower unemployment and welfare costs than the Italian average, both regions are large net contributors to a central state widely regarded as inefficient at best.
Veneto president Luca Zaia says 30 billion euros (USD 35 billion) are wasted every year at a national level and fiscal rebalancing will be a top priority for him and his Lombardy counterpart Roberto Maroni if the votes go their way.
Lombardy sends 54 billion euros more in taxes to Rome than it gets back in public spending. Veneto's net contribution is 15.5 billion.
The two regions would like to roughly halve those contributions -- a concession the cash-strapped state, labouring under a mountain of debt, can ill afford.
They also want new ones relating to security issues and immigration -- steps which would require changes to the constitution.
The referendums could have a domino effect -- a similar autonomy vote is being debated in Liguria, the region that includes the Riviera coastline, and Emilia Romagna, another wealthy industrial part of the country, is already trying to negotiate more devolved powers.
Economist Lorenzo Codogno says that while Italian unity is not under threat, today could mark the opening of a Pandora's box.
Although the referendums have been driven by the Northern League, which has long abandoned the secessionist principles on which it was founded, the Yes campaign is backed by most of the centre right and sections of the centre left.
Milan's mayor Giuseppe Sala, a member of the ruling Democratic Party, says greater self-rule "is an idea shared by everyone, not one that belongs to the League."
There is also a substantial body of opinion that regards the votes as unnecessary extravagances: organising them will cost 50 million euros in Lombardy and 14 million euros in Veneto.
In a first for Italy, voting in Lombardy will be conducted on computer tablets. Acquiring them raised the cost of the ballot but should ensure an early result after polls close at 11 pm (2100 GMT).
Disclaimer: No Business Standard Journalist was involved in creation of this content
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