The school was housing nearly 3,000 internally displaced people in Rafah in southern Gaza.
"The dead and wounded in Rafah are still under the rubble and in the streets," Health Ministry spokesman Dr. Ashraf el-Qedra said.
Witnesses told The New York Times people were waiting in line for food when the missile struck.
Chris Gunness, a spokesman for the U.N. Relief and Works Agency told CNN there were "multiple deaths and injuries in the vicinity of the school."
"I am not saying it was a direct hit, and we are not confirming who it's by yet. We hope to have more details later," he added.
Israel Defense Forces hasn't commented on the attack.
Since fighting began July 8, 1,839 Palestinians have been killed -- mostly civilians -- and 67 Israelis, including three civilians.