This species is characterized by its robust habit (for Palicourea); medium-sized to usually robust leaves; stipules with broadly triangular to ligulate, obtuse to rounded lobes and a sheath that begins as concave then widens into subtruncate; well developed stout peduncles; well developed narrowly pyramidal to cylindrical, paniculiform red to yellow inflorescences with ca. 10-25 pairs of branched secondary axes; short calyx limbs; tubular medium-sized yellow to red corollas that are externally densely puberulous with stout colored trichomes; and ovoid rather small fruits with 4-5 pyrenes. The inflorescence are erect and showy. This species is common and striking.

Palicourea grandifolia is similar to Palicourea guianensis, which however has a usually smaller habit, medium-sized to somewhat smaller leaves, pyramidal to broadly pyramidal inflorescences, often longer corollas, and mostly 2-locular ovaries and fruits. Plants of Palicourea guianensis from the Guianas and northwestern Amazonia, however, vary in locule number, with ovaries usually 3-4-locular and fruits with 3-4 pyrenes. The separation of these species thus is not clear based on any fully discrete characters, as Steyermark (1972, 1974) noted in his keys.

Steyermark separated two varieties of Palicourea grandifolia based on averaged details of the leaf pubescence (e.g., "lower surface of leaf glabrous or nearly so" vs. "usually pubescent"). He reported both of these from basically the same geographic range in Brazil and Venezuela, and did not study specimens from other countries. These are less easily separated now with more specimens available, and are not recognized here.

Palicourea grandifolia is also similar to Palicourea sellowiana, which is found in eastern Brazil and differs in its longer inflorescences with usually more numerous and slender secondary axes, corollas externally glabrous or hirtellous with colorless trichomes, 2-locular ovaries, and fruits with 2 pyrenes.