This species can be recognized by its robust habit, leaves that are white-canescent below, stipules that are so deeply divided they appear to be four free stipules, and large inflorescences with rather large yellow to red flowers that are bearded or densely hairy at the throat. The flowers are apparently diurnal, and at least sometimes are pollinated by hummingbirds (Olivier Gaubert, pers. comm.). This species is widespread and rather variable in morphology.
This species is similar to Isertia laevis, and these have sometimes been confused (most notably by Dwyer in the Flora of Panama Rubiaceae). These species both have robust habits, leaves that are white-canescent below, and flowers of similar size and form. However I. hypoleuca has red to yellow flowers and drupaceous fruits with 5-6 locules, vs. berries 2-3 locules in I. laevis. Isertia hypoleuca is also similar to I. verrucosa, in particular in its robust habit and large white flowers; however I. verrucosa differs in its berry fruits with 2-3 locule.