The blaze started at the corner of St. Isaac's Square and Yakubovich Street, next to St. Isaac's Cathedral, according to Fontanka, Bumaga and TV Rain, which cited readers.
A column of smoke could be seen from various districts of the city, Ekho reported, citing Bumaga and Fontanka.
The Miller Mansion is a historic building that was slated to be redeveloped into luxury housing, according to Meduza.
The cause of the fire has not been stated. Details are being clarified.