Going to Rome in 1545 Titian met Michelangelo, Sebastiano del Piombo, Pietro Bembo and Cardinal Alessandro Famese. Given honorary Roman citizenship he painted Pope Paul Ill with his grandsons Alessandro and Ottavio (1546) - a work of rare psychological insight displaying the tensions foretelling the eventual schism between the sitters. Returning to Venice there followed the Votive portrait of the Vendramin Family (1547) of original composition set in the open. Gabriel and Andrea Vendramin worship in the open with Andrea's sons but suprisingly Andrea's six daughters are excluded. No other Titian is comparable to such a large family group which was not common in Renaissance portraiture.

In 1548 Charles V invited Titian to Augsburg where he painted the posthumous Isabella of Portugal (1548) showing her richly dressed and spiritually calm. Isabella, dead wife of Charles V, is created in poetic effect as an act of memory showing her as remote in depiction as she is in death.