Five-year-old British brain tumour patient Ashya King left for Spain from Prague on Sunday, said a spokeswoman for a Prague medical centre where the boy had received special proton therapy.
"He left for Malaga on a regular flight. Everything went as planned," said Proton Therapy Centre spokeswoman Iva Tatounova.
Ashya King, whose case made headlines after his parents had snatched him from a British hospital against the doctors' will in August, spent almost 50 days in Prague.
He underwent 30 sessions of proton therapy with a beam targeting his brain tumour in the Czech capital, and doctors say he now has about a 70 percent chance of recovery.
After being admitted to the proton centre in a frail state in early September, Ashya can now eat on his own, sit up, play and even walk a few steps.
He is due to undergo further treatment, possibly chemotherapy, in Spain where his family owns a house.
Ashya's parents snatched the boy from Southampton General Hospital in England in August, sparking an international manhunt.
The Kings feared that traditional radiotherapy would damage his brain and opted instead for the proton therapy, unavailable in Britain but touted as more precise, as it targets only malignant cells.
The Kings were taken into custody in Spain on an international warrant, after British authorities suspected they were not acting in the best interests of the child.
But after the couple spent four days in a Spanish prison, a British court reunited them with their son in a Spanish hospital and allowed them to travel to Prague for the treatment.
The case received substantial coverage in the British media, with public opinion shifting from outrage to sympathy for the parents.
British prosecutors have dropped the case against them after acknowledging that Ashya had been properly cared for.
But Ashya's father Brett King has said it would take the family some time to pluck up the courage to return to England.