The blast caused by an explosive device "on or in the vehicle" occurred during morning rush-hour traffic on Bismarckstrasse, within sight of the Victory Column monument.
The explosion flipped over the vehicle, leaving its front severely dented and debris strewn several metres away.
No other injuries were reported, although the car rammed into a parked vehicle.
Identifying the victim as a 43-year-old man, Berlin police said on Twitter: "There is currently no indication that this was linked to terrorism."
Spiegel Online said the victim had previously been investigated by police for offences including drug trafficking and that investigators believe today's attack was linked to organised crime.
The Volkswagen Passat station wagon was heading downtown when the explosion struck close to the subway entrance to Deutsche Oper station, in front of one of Berlin's three opera houses.
Police had asked residents to stay indoors and keep their windows shut. They later gave the all-clear after completing a sweep for further explosives.
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