A religious pilgrimage for some, an architecture/art-history mecca for others, the Vatican museum—the beating heart of Vatican City and all of Rome, really—is at the tippy top of the must-see list. The museum is a catch-all for the Sistine Chapel (famously covered in works by Michelangelo and Botticelli among others), St. Peters Basilica, the Vatican gardens, and so much more—meaning that once you take wait-times into account, a visit can easily turn into an all-day situation, so plan accordingly. Avoiding weekends, hiring a private guide, or booking an off-hours tour are all good ways to go.

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