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A pivotal step forward in chemical approaches to controlling gene expression is the development of sequence‐specific DNA‐binding molecules that can enter live cells and traffic to nuclei unaided. DNA‐binding polyamides are a class of programmable, sequence‐specific small molecules that have been shown to influence a wide variety of protein–DNA interactions. We have synthesized over 100 polyamide‐fluorophore conjugates and assayed their nuclear uptake profiles in 13 mammalian cell lines. The compiled dataset, comprising 1300 entries, establishes a benchmark for the nuclear localization of polyamide‐dye conjugates. Compounds in this series were chosen to provide systematic variation in several structural variables, including dye composition and placement, molecular weight, charge, ordering of the aromatic and aliphatic amino‐acid building blocks and overall shape. Nuclear uptake does not …