A systematic revision of the Epipetrum group of Dioscorea (Dioscoreaceae), which traditionally included three taxa endemic to Chile, is presented. We evaluated the taxonomic value of macro- and micromorphological traits to delimit generic boundaries with respect to other yams and to identify and separate its taxa. The comprehensive survey included 10 qualitative and 43 quantitative traits related to all plant organs and new microanatomical features of leaf, fruits, seeds, and pollen. Discriminant analyses were conducted with three accumulative morphological data sets to test seven taxonomic hypotheses of differentiation among taxa. Our results indicate that these taxa are characterized by the combination of prominent pistillodes in male flowers and a base chromosome number of x = 7, which separate it from all other Dioscoreaceae, plus different sets of morpho-anatomical traits that differentiate it from other putatively closely related yams with unwinged seeds in Dioscorea (the Borderea group, the Nanarepenta group, the Tamus group, etc.). Dioscorea biloba is the most distinctive species. Our analyses revealed significant morphological differences between northern and southern populations of this species resulting in the recognition of two subspecies, the northern D. biloba subsp. biloba, and the new southern D. biloba subsp. coquimbana. Dioscorea humilis and D. polyanthes are morphologically similar and only differ in qualitative leaf traits. This minor variation is better treated by reducing D. polyanthes to subspecific rank in D. humilis, and the combination D. humilis subsp. polyanthes is made herein.