The cocaine, seized in raids in July, was found to have gone missing from a secure room yesterday in the latest major embarrassment for the Paris police.
Sniffer dogs were deployed and many people are being questioned by a team from the national police's internal affairs division.
"If the investigation shows that the law has been broken...Very firm measures will be immediately taken," police said in a statement.
The cocaine was seized in raids that saw the arrest of several people, mainly Senegalese nationals.
The cocaine was stored in a secure room at the police headquarters but there was no close circuit television in the area.
A source close to the investigation said only three people had keys to the room.
Several policemen were being questioned, a source said. Many of those working there told AFP they were astounded at the disappearance and said they did not believe it was pilfered.
"It will be a thunderbolt if theft is proved," said one police source.
Another spoke of several possible scenarios evoking "internal tensions" within the organisation and possible "score settling".
The revelations are a major embarrassment for the Paris criminal police, whose headquarters overlooking the Seine and located near the famed Notre Dame cathedral have been immortalised in several books and films.
The headquarters attracted unwelcome attention in April when two elite French police officers were charged with raping a Canadian tourist there in a case that has sent shockwaves across France.
The 34-year-old woman said she was raped in the police headquarters at night after meeting the officers during a night of heavy drinking at an Irish pub.
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