Gunmen attacked the College of Agriculture in Gujba, Yobe state, in the early hours and shot students when they were asleep, sources said.
College provost Molima Idi Mato confirmed the casualty figure at 50, but added the death toll could be higher as more bodies were being recovered.
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More than a thousand students have fled the institution, which was also set on fire by the attackers, said state military spokesman Lazarus Eli.
Schools and universities in Yobe state have been the target of attacks, all blamed on Boko Haram, which has vowed to install an Islamic government in the country and killed hundreds in its four-year insurgency.
At least 143 people had been killed this month in the northeastern state of Borno by suspected Boko Haram militants who came disguised as soldiers, set up checkpoints and fired on motorists and bystanders.
Yobe was among the three states where President Goodluck Jonathan declared a state of emergency in May and ordered an operation against the Islamist sect.
Many militants fled their bases in the northeast, the insurgents' traditional stronghold, and violence initially fell, but revenge attacks quickly followed.
In June, Boko Haram carried out two attacks on schools in the region. A month later, Islamists threw explosives and sprayed gunfire into dormitories in the town of Mamudo in Yobe, killing 41 students.
Boko Haram regards schools as a symbol of Western culture. The group's name translates as "Western education is forbidden".
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