The deadly fire snarled traffic in Boston's densely populated Back Bay neighborhood. At least five firefighters were injured. Fire department spokesman Steve MacDonald said a roll call was being done to make sure all firefighters were accounted for.
City Councilor Josh Zakim, who represents the area, confirmed the two firefighters' deaths.
Major thoroughfare Storrow Drive was shut down for a time, and people were being asked to stay out of the area.
EMS spokesman Nick Martin said 18 people were taken to hospitals. MacDonald said there were no reports of residents missing and it appeared everyone who was inside at the time had escaped.
An assistant district attorney was being sent to the scene, standard procedure in cases in which there are serious or potentially life-threatening injuries or deaths, said Jake Wark, a spokesman for Suffolk District Attorney Dan Conley. There was no immediate word on the cause of the fire.
Despite strong winds and cold temperatures, people gathered to watch firefighters work from outside the building.
"The smoke was unbelievable," said Kayla Dasilva, who lives a few blocks away and went with her roommate to see what was happening.