A group of gunmen dressed in camouflage clothing opened fire on crowds in in the Crocus City Hall music venue near Moscow.
It is believed the group was made up of up to five people, who used automatic weapons on Friday evening.
Russia's top domestic security agency, the Federal Security Service, said there are dead and wounded but didn't give any numbers.
Several news sites and social media accounts have reported hearing a second blast at the scene, where 50 ambulance crews have already been sent.
Russian news reports said that the assailants threw explosives, triggering a massive blaze.
In video clips, flames can be seen reaching the sky while plumes of black smoke rise above the venue.
The attack took place as crowds gathered for a concert of Picnic, a famed Russian rock band, at the hall that can accommodate over 6,000 people.
Although visitors were evacuated, an unspecific number of people have been trapped by the blaze, local media reports.
A helicopter has reportedly been called to help put the fire out.Moscow Mayor Sergei Sobyanin said: "A terrible tragedy occurred in the shopping center Crocus City today.
"I am sorry for the loved ones of the victims."
Mr Sobyanin has also cancelled all mass gatherings for the weekend, while security at Moscow’s airports and train stations has been tightened.
In one unverified video posted on social media, men with automatic weapons were shown firing repeatedly at screaming civilians, including women, who were cowering below what looked like an entrace sign.
Other video footage showed a number of people lying motionless in pools of blood outside the hall.
White House National Security Advisor John Kirby said Friday that he couldn't yet speak about all the details but that "the images are just horrible. And just hard to watch.""Our thoughts are going to be with the victims of this terrible, terrible shooting attack," Kirby said. "There are some moms and dads and brothers and sisters and sons and daughters who haven't gotten the news yet. This is going to be a tough day."
The US embassy in Russia warned earlier this month that "extremists" had imminent plans for an attack in Moscow.
Officials gave no specific details about the threat but said that people should avoid concerts and crowds and be aware of their surroundings.
Just before this, Russia's Federal Security Service, the main successor to the Soviet-era KGB, said it had foiled an attack on a synagogue in Moscow by a cell of the militant Sunni Muslim group Islamic State.
It was unclear if the two statements were linked.
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