A fifteenth century panel painting, Virgin and Child with Four Angels Playing Musical Instruments, attributed to the Florentine painter Apollonio di Giovanni, was the subject of a technical examination and subsequent conservation treatment. Analysis of the paint layers revealed that certain pigments had changed optically and chemically from their original colors. This was due to both the aging of the painting materials and the effects of earlier restoration procedures. During the conservation and restoration of the panel, it became evident that compositional features of the image had been altered by extensive overpaint. As well, the badly yellowed varnish layer significantly altered the tonality of the work. A comparison of the painting with several cassone panels attributed to Apollonio and his assistants produced valuable evidence concerning the working techniques of the shop. This technical evidence strongly supports the present attribution of this panel to Apollonio di Giovanni.