How do I open the safe at Gio's Apothecary?
Have you found the safe and got rid of its guardian? If not, come back when you have.
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You'll need a hint for the safe combination.
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Go out and explore the island until you've found it.
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Have you visited the Ship Sculpture lately? It's an actual ship now, or the beginnings of one.
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Look at the SIGN next to the ship hull.
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Specifically at the DRAWING scratched out on the side.
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Do you know the combination now?
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The Duchess has none. What is it? (Disclaimer: Any resemblance to a real duchess is purely coincidental.)
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Heart. So 1 refers to "heart."
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2 points to her crown. She has many of those. What are those?
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Diamonds. So 2 is "diamond."
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3 points to her ...
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"Club."
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And what does she dig holes with?
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That would be her "spade."
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Go back to the safe and rotate the dials until you have heart-diamond-club-spade.
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Turn the handle to open and get the strange device piece from inside.