"The flight controllers contacted the pilot (with the plane) at a height of 37,000 feet (near Athens)... He did not mention a problem," civil aviation chief Constantinos Litzerakos told Antenna TV.
Litzerakos said the controllers had last spoken to the pilot "around 0005 GMT", some 25 minutes before the plane disappeared from Greek radar.
A civil aviation statement said the pilot "was in a good mood and gave thanks in Greek when authorised to exit the Athens flight information region.
The plane vanished from radar screens at 0029 GMT after crossing into the Cairo flight information region, the Greek civil aviation statement said, referring to Egyptian air space.
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A civil aviation source told AFP the plane's last location was "around 130 nautical miles off the island of Karpathos" which is situated between Crete and Rhodes.
The Greek defence ministry said it had dispatched two search planes and a frigate to international waters in the area, with additional resources on standby on Karpathos and nearby Crete.
EgyptAir said contact was lost with the flight about 280 kilometres (175 miles) north of the Egyptian coast.
Neither the Greek coastguard nor the navy could confirm reports that a passing ship had seen "a ball of fire in the sky".
The civil aviation chief said if there had been an explosion, any debris would have scattered across a wide distance.
"It was at a height of 37,000 feet, dispersal is quite logical. This is quite an altitude," he told Antenna.