Chronic progressive lymphedema (CPL) is a debilitating condition identified in Clydesdales, Shires and Belgian draft horses and results in progressive swelling of the lower legs associated with the development of thick skin folds, ulcerations, fibrosis and marked hyperkeratosis. The result is severe discomfort and recurrent secondary infection, often requiring euthanasia. Due to the delayed onset, many horses are bred prior to diagnosis. CPL has only been documented in three related draft horse breeds, suggesting a genetic cause. Determining the molecular basis would enable owners to test horses prior to breeding and facilitate the elimination of CPL. Mutations in the FOXC2 gene cause a comparable condition in humans, lymphedema-distichiasis. This gene was sequenced in affected and unaffected draft horses and a control horse. Four single nucleotide polymorphisms (SNPs) were identified in unaffected draft horses and the control horse, indicating that they were not associated with CPL. A fifth SNP was seen in a single affected draft horse and the control horse. Since it was not seen in all affected draft horses, this SNP is not associated with the CPL phenotype.