Two men have been arrested on suspicion of murdering seven-year-old Toni-Ann Byfield in September 2003, police said.
Toni-Ann is thought to have witnessed a murder
They are also being questioned in connection with the murder of convicted drug dealer Bertram Byfield in Harlesden, north-west London.
The suspects, aged 31 and 22, were arrested in Merseyside and north-west London respectively.
A 28-year-old woman was also arrested on suspicion of assisting an offender and supplying class A drugs.
All three are being questioned in London.
To date, five people have been arrested in the police inquiry but all have been released without charge.
The schoolgirl is thought to have been shot after witnessing the murder of Mr Byfield, whom she thought was her father, to stop her identifying the gunman.
Toni-Ann had only been in London a few weeks and had previously been in the care of Birmingham social services, where she had been placed with a foster family.
She had been allowed to visit Mr Byfield while they were on holiday.
Both were found dead in a bed-sit at a block of flats in Harrow Road just after midnight on 14 September 2003.
There is a £25,000 reward for any information leading to the arrest and prosecution of the killers.