Firefighters have saved snakes, lizards and turtles from a classroom fire in Lilydale overnight.

Emergency services were called to Lilydale Highschool on Melba Avenue just after midnight where a portable classroom was ablaze.  

CFA Regional Duty Officer Don Tomkins said it was an unusual scenario and some firefighters were tentative about dealing with snakes.

"They knew on arrival it was the reptile room, which made them more cautious," Mr Tomins said.

"The reptiles didn't pose any danger to us but still, a number of people are very uncomfortable with snakes at any time."

It took 40 firefighters around 45 minutes to extinguish the blaze.

Mr Tomkins said the room held around 50 tanks of reptiles and firefighters assisted a school staff member to capture and relocate the animals.

It's understood the reptiles are part of a school program in animal handling and wildlife care.

Some reptiles did not survive, Mr Tomkins said.

The cause of the fire will be investigated but isn't being treated as suspicious.