The raid at 2:00 am (0630 IST) targeted the Federal Government College in the town of Buni Yadi in Yobe state and bore the hallmarks of a similar attack last September in which 40 died.
The attackers reportedly hurled explosives into student residential buildings, sprayed gunfire into rooms and hacked a number students to death.
A senior medical source at the Sani Abacha Specialist Hospital in Yobe's capital Damaturu said the gunmen only targeted male students and that female students were "spared".
Yobe has been one of the hardest areas in Boko Haram's four-and-half year Islamist uprising, which has killed thousands of people.
The name Boko Haram means "Western Education is forbidden".
The group has been blamed for waves of school attacks, especially in Yobe, where scores of students have been slaughtered in the last year.
The state's police chief, Sanusi Rufai, who confirmed the attack and had given an earlier death toll of 29, was headed to Buni Yadi, roughly 60 kilometres from Damaturu, with Governor Ibrahim Geidam to assess the damage.
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