An elderly priest was killed with a cut to the throat by two assailants claiming to be from ISIS, and another hostage was badly injured.
The attackers were killed by the security forces.
"The pope has been informed and participates in the pain and horror due to this absurd violence, with condemnation of the most radical form of hate and prayer for the people hit (by it)," Lombardi said.
"It is another terrible piece of news, which unfortunately is added to the series of violence that has already shocked us, creating immense pain and concern.
"We are following the situation and await further information to understand what has happened.
"We are close to the church in France, to the archdiocese of Rouen, to the community that has been hit and to the French people.
"We are particularly shocked because this horrible violence took place in a Church, in which God's love is announced, with the barbarous killing of a priest and the involvement of the faithful".
Francis is praying to God to inspire "reconciliation", according to a telegram sent on his behalf to the Archbishop of Rouen Dominique Lebrun following Tuesday's attack.
"May the Lord inspire everyone to thoughts of reconciliation and fraternity in this new test," read the telegram, signed by Vatican Secretary of State Pietro Parolin.
"The Holy Father is particularly disturbed by the fact that this act of violence took place during a Mass, a liturgy that implores God to give his peace to the world".
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