Rogier created another great work during his early period in Brussels, roughly between the middle of the 1430s and the beginning of the 1440s: the painting of St Luke Drawing a Portrait of the Virgin, known as the St Luke Madonna. St Luke the Evangelist was also the first Christian painter, and had painted the Virgin Mary from life. As a consequence he was the patron saint of painters, and in many towns and cities was regarded as patron of their guilds. As a result, most of the major pictures of St Luke were destined for the altars of these communities; Rogier's painting was probably an altarpiece for the Brussels guild.

There exist several examples of this composition, identical apart from a few details, of which the one in the Museum of Fine Arts in Boston, since its restoration in 1932-33, is regarded by most art historians as the original (other examples in Munich, Alte Pinakothek, St Petersburg, Hermitage, and Bruges, Groeninge Museum).

Preview	Picture Data	Info
	St Luke Drawing a Portrait of the Madonna 1435 Oil and tempera on panel, 138 x 111 cm Museum of Fine Arts, Boston
	St Luke Drawing a Portrait of the Madonna (detail) 1435 Oil and tempera on panel Museum of Fine Arts, Boston
	St Luke Drawing a Portrait of the Madonna - Oil on canvas transferred from wood, 103 x 109 cm The Hermitage, St. Petersburg
	St Luke Drawing a Portrait of the Madonna (detail) - Oil on canvas transferred from wood The Hermitage, St. Petersburg
	St Luke Drawing a Portrait of the Madonna (detail) - Oil on canvas transferred from wood The Hermitage, St. Petersburg
	St Luke Drawing a Portrait of the Madonna (detail) - Oil on canvas transferred from wood The Hermitage, St. Petersburg
	St Luke Drawing the Portrait of the Madonna c. 1450 Oil on oak panel, 138 x 110 cm Alte Pinakothek, Munich
	St Luke Drawing the Portrait of the Madonna c. 1450 Oil on oak panel Alte Pinakothek, Munich
	St Luke Drawing the Portrait of the Madonna - Oil on oak panel, 133 x 107 cm Groeninge Museum, Bruges