Former Orange Prize winner Ann Patchett could pick up the prestigious literary prize for a second time after she was nominated again 10 years after she first won.
The American novelist, who won with Bel Canto in 2002, has been nominated for her sixth novel, State Of Wonder, which is the story of a secretive scientist developing a wonder drug in the depths of the Brazilian rainforest.
Also on the shortlist for the prize, which recognises the best novel written in English by a woman, are Dubliner Anne Enright, Canadian Esi Edugyan, whose Half Blood Blues was shortlisted for the Man Booker Prize, and Londoner Georgina Harding.
Completing the line-up are two Americans - debut novelist Madeline Miller, and Cynthia Ozick who is nominated for her seventh novel.
Writer Joanna Trollope, who chaired the judging panel, said it was "a shortlist of remarkable quality and variety".
She said: "It includes six distinctive voices and subjects, four nationalities and an age range of close on half a century. It is a privilege to present it.
"My only regret is that the rules of the prize don't permit a longer shortlist. However, I am confident that the 14 novels we had to leave out will make their own well-deserved way."
The other judges include BBC 5 Live presenter Victoria Derbyshire, newsreader Natasha Kaplinsky and writer Lisa Appignanesi.
The winner will be presented with a cheque for £30,000 and a limited edition bronze statue known as the Bessie at an award ceremony at London's Royal Festival Hall on May 30.
Previous winners include Zadie Smith, Linda Grant, Andrea Levy and Tea Obreht, who became the youngest ever winner last year at the age of 25.
Jonathan Ruppin, web editor of Foyles bookshops, said he was tipping Harding to win.
He said: "It's an absorbing shortlist and just what literary prizes, and in particular the Orange Prize, are all about: nudging readers towards something unfamiliar but very special.
"These are all authors with the potential to delight many more readers than they currently have, even Anne Enright with her Man Booker win in 2007.
"There are some exceptional writers who've not made the cut, but that's down to the strength of the competition - the judges must have found it really tough this year."