The flowers of Seneca Snakeroot have a bud-like appearance even when they are open. For this species, there is some significant variability in the width of the leaves and the size of the seed capsules and their seeds. In Illinois, other Polygala spp. (Milkworts) have non-white flowers or their leaves are whorled, rather than alternate. They also tend to be smaller in size overall than Seneca Snakeroot. Therefore, it is fairly easy to distinguish Seneca Snakeroot from these other species. This species also superficially resembles some Persicaria spp. (Smartweeds) with white flowers, however the latter have conspicuous ochreae (sheaths) that wrap around their stems and they prefer wetter habitats. Seneca Snakeroot also has floral racemes that superficially resemble those of Orbexilum pedunculatum (Sampson's Snakeroot), but the latter species can be easily distinguished by its trifoliate leaves.
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