Christ carries the cross, on his way to Golgotha. Behind him is Simon of Cyrene, who helps to bear the weight of the cross. The fainting Virgin is supported by the three other Maries. Saint John the Evangelist, beside her, wrings his hands.
The painting formed the central panel of the predella below an altarpiece of the Virgin and Child with Saints, known today as the 'Colonna Altarpiece'. It was made for the Church of Santa Antonio, Perugia, in about 1504-5. The centre panel, surmounted by a lunette, as well as a part of the predella, are now in New York (Metropolitan Museum of Art). Other parts of the predella are in Boston (Isabella Stewart Gardner Museum), and London (Dulwich Picture Gallery).