The blaze started in an electrical room at the five-star Palafitte hotel, 2 Route des Gouttes d’Or, around noon, Neuchâtel cantonal police said.
Eight fire fighters attended and rapidly doused the flames, police said.
No one was injured in the fire.
People were evacuated from the hotel’s restaurant and rooms because of smoke, police said.
The canton’s chief prosecutor launched an investigation into the cause of the fire.
With rooms costing up to 1,040 francs a night, the “designer” Palafitte hotel consists of rooms in futuristic modules.
Twenty four of the 40 rooms are built on stilts over the lake, offering unobscured water and mountain views from balconies.
Elsewhere, another fire early Tuesday in the village of Attalens in the canton Fribourg caused significant damage to a 13-unit apartment building.
Emergency officials were alerted around 3.45am after the building’s roof caught fire, Fribourg newspaper La Liberté reported online.
Three residents suffered from smoke inhalation while a fourth experienced a “malaise,” La Liberté said.
Residents were evacuated but 16 tenants have had to be re-lodged, police said.
The roof of the building was being renovated.
An investigation is under way into the cause of the fire.