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Should Illustrator be set to CMYK or RGB mode when using Pantone colors? Thanks in advance!

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CMYK.

The Pantone matching system is a print production ink system. Print production always uses CMYK as a basis. Pantone colors have absolutely no basis in the RGB spectrum.

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When doing anything for print, you should use CMYK. RGB colors have a much wider gamut, so what you see on screen might look more vibrant, but it won't print that way, especially when directly translating a print-only color model to a screen-only color model. Even software-performed RGB -> CMYK and the reverse can be iffy sometimes.

You also have to take into account that CMYK colors will look comparatively dull on a monitor to anything else on screen because of the color gamut difference; on a printed product, the audience will only be seeing colors within the CMYK spectrum, so it won't be out of place or expectation.

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