Gunmen in southern Yemen stormed a retirement home run by a charity established by Mother Teresa, killing 16 people, including four Catholic nuns.
Two gunmen secured the home for the elderly in Aden, while four others entered the building on the pretext that they wanted to visit their mothers, according to the charity, Yemeni security officials and witnesses.
The gunmen then moved from room to room, handcuffing the victims before shooting them in the head. A nun who was rescued by locals said she hid inside a fridge in a storeroom after hearing a Yemeni guard shouting "run".
Vatican Secretary of State, Cardinal Pietro Parolin, said Pope Francis was "shocked and profoundly saddened" by the attack.
Francis "prays that this pointless slaughter will awaken consciences, lead to a change of heart, and inspire all parties to lay down their arms and take up the path of dialogue".
The statement said: "In the name of God, he calls upon all parties in the present conflict to renounce violence, and to renew their commitment to the people of Yemen, particularly those most in need, whom the Sisters and their helpers sought to serve.
"Upon everyone suffering from this violence, the Holy Father invokes God's blessing, and in a special ways he extends to the Missionaries of Charity his prayerful sympathy and solidarity. "
Sunita Kumar, a spokeswoman for the Missionaries of Charity in the Indian city of Kolkata, said the members of the charity were "absolutely stunned" at the killing.
"The Sisters were to come back but they opted to stay on to serve people" in Yemen, she added.
She also said that two of the killed nuns were from Rwanda and the others were from India and Kenya.
There were around 80 residents living at the home, which is run by Missionaries of Charity, an organisation established by Mother Teresa. Missionaries of Charity nuns also came under attack in Yemen in 1998 when gunmen killed three in the Red Sea port city of Hodeida.
Islamist militants are being blamed.