Official state news agency SANA said a second suicide blast struck a restaurant in the Rabweh district of the Syrian capital, leaving an unknown number of casualties.
The bombing inside the historic Justice Palace - near the crowded Hamidiyeh market - is the latest in a spate of deadly explosions and suicide attacks targeting government-controlled areas in Syria.
Damascus police chief Mohammad Kheir Ismail said the Justice Palace attacker was wearing a military uniform and carrying a shotgun and grenades and arrived at the entrance to the building at around 1.20pm.
He was stopped by guards, who removed his weapon and asked to search him.
At that point, the man hurled himself inside the building and detonated the explosives, the police chief told state TV.
Another 45 people were wounded in the blast, which is believed to have been timed to kill lawyers, judges and other people going into the building.
In the second attack, a suicide bomber killed several people inside a restaurant in Rabweh district.
Ikhbariyeh TV said the attacker was chased by security guards, before rushing inside the restaurant and detonating an explosive vest.
It comes as airstrikes killed 20 people, at least 14 of them children, in Idlib on Wednesday, according to the Britain-based Syrian Observatory for Human Rights.
The group said the aircraft behind the attack, believed to be Russian, struck the city and the town of Maarrat Misrin.
More than 400,000 people have been killed and millions more displaced since the conflict began in Syria in March 2011, when a popular uprising against President Bashar al Assad descended into a civil war.
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The recent attacks have targeted highly symbolic sites, and could herald the start of a new insurgency campaign by al Qaeda-linked militants.
On Saturday, twin attacks near holy shrines frequented by Shia Muslims in Damascus killed at least 40 people. They were claimed by the al Qaeda-linked group known as the Levant Liberation Committee - formerly the Nusra Front.
Peace talks have been taking place in the Kazakhstan capital Astana, but Syria's armed opposition has boycotted the most recent round over what it claims is ongoing government military offensives in the country.
The talks, brokered by Russia and Turkey, centre on reaching a ceasefire in Syria and getting humanitarian aid to millions of civilians.
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