The blast happened during early morning prayers at the Madina mosque in the Unguwar Shuwa area of Mubi, some 200 kilometres (125 miles) by road from the Adamawa state capital Yola.
Security analysts said Tuesday's bombing again underlined the threat posed by Boko Haram, despite an overall decline in deaths from attacks by the group last year.
Adamawa state police spokesman Othman Abubakar told AFP that at least 50 were killed in the Mubi attack.
"It was a (suicide) bomber who mingled with worshippers. He entered the mosque along with other worshippers for the morning prayers.
"It was when the prayers were on that he set off his explosives."
Asked who was responsible, Abubakar said: "We all know the trend. We don't suspect anyone specifically but we know those behind such kind of attacks."
Roof blown off
The attack bore all the hallmarks of Boko Haram, the Islamist militants whose insurgency has left at least 20,000 people dead and more than 2.6 million others homeless since 2009.
Haruna Furo, head of the Adamawa state emergency management agency, and Musa Hamad Bello, chairman of the Mubi north local government area, both confirmed the attack.
They gave lower death tolls but both said the number killed was likely to rise.
Another emergency services official described the blast as "devastating" and said there were "high casualties".
Abubakar Sule, who lives near the mosque, said he was present during the rescue operation and that 40 people died on the spot while several others were taken to hospital with severe and life-threatening injuries.
"The roof was blown off. People near the mosque said the prayer was mid-way when the bomber, who was obviously in the congregation, detonated his explosives.
"This is obviously the work of Boko Haram."
Yan St-Pierre, a counter-terrorism specialist at the Modern Security Consulting Group in Berlin, said the bombing fitted a pattern of previous attacks.
"It fits with the increasing lethality and potency of suicide attacks of the organisation's current 'hot streak', which started approximately four weeks ago," he said.
The latest Global Terrorism Index, published last week, said that deaths attributed to Boko Haram in 2016 fell by 80 percent.
But St-Pierre said despite this "Boko Haram remains an extremely potent and dangerous organisation" which was far from being "on the back foot", as the military has claimed.
In October 2012, at least 40 people were killed in an attack on student housing in Mubi that was widely blamed on Boko Haram.
In June 2014, at least 40 football supporters, including women and children, died in a bomb attack after a match in the Kabang area of the town.
Boko Haram briefly overran Mubi in late 2014 as its fighters rampaged across northeastern Nigeria, seizing towns and villages in its quest to establish a hardline Islamic state.
The town's name was changed temporarily to Madinatul Islam, or "City of Islam" in Arabic, during the Boko Haram occupation.
But it has been peaceful since the military and the civilian militia ousted them from the town, which is a commercial hub and home to the Adamawa State University.
Yet in recent months, Boko Haram activity has been concentrated around Madagali, in the far north of Adamawa near the border with neighbouring Borno state.
There have been repeated raids and suicide bombings, blamed on Boko Haram remnants pushed out of their camps in the Sambisa Forest area of Borno.
Boko Haram fighters are also said to be hiding in the Mandara mountains, which forms the border of Adamawa and Nigeria with neighbouring Cameroon, where there has also been more attacks.
Ryan Cummings, from security analysts Signal Risk, said the attack suggests Boko Haram "has an active operational presence in Adamawa" and retained the capacity to hit hard.
"It appears that despite open calls for Boko Haram to desist in such acts of mass violence against Muslim civilian interests, that these have not been heeded," he added. (AFP)