The recent restoration of the Saint Sebastian by Lorenzo Lotto in a private collection in Bologna makes it possible to clarify its origin, together with that of Saint Roch in the National Gallery in Urbino. Both are what remains of a not very large canvas, formerly in the church of Santa Maria in Posatora in Ancona, painted in 1549, as the artist himself attests in the Libro di spese diverse conserved in the Archive of the Holy House of Loreto. Linking up with the previous research by Mauro Lucco and Peter Humfrey, the essay discusses the relationship with two other images of the Saint Sebastian painted by the artist (one in the Gemäldegalerie in Berlin, the other in the Holy House), suggesting a symbolic reading for some details recognisable in them.