Georgia O'Keeffe's White Calla Lily is to headline Sotheby's American Art sale in New York on May 20.
The piece is expected to make around $8m-12m.
Sotheby's comments: "Between 1918 and 1932 O'Keeffe executed over 200 flower paintings, but it was arguably in the calla lily that the artist found her ideal motif, one that provided the perfect synthesis of subject and form that now defines her most celebrated work.
"The artist clearly held the present painting in high regard, as she kept it in her personal collection until her death in 1986."
Last year O'Keeffe's Jimson Weed/ White Flower No 1 set a new world record for a female artist at auction after it sold for $44.4m.
This was significantly higher than the previous record, which stood at $11.9m for an untitled painting by Joan Mitchell. The present lot is therefore likely to become the second most valuable painting by a woman ever to come to auction.
The sale will also include work from Milton Avery, Norman Rockwell and John Singer Sargent.
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