There is broad consensus that the isthmus of Panama closed around 3.7–2.8 Mya in the Pliocene. The most compelling evidence is the Great American Biotic Interchange, which according to the fossil record commenced less than 3 Mya. However, recent studies have proposed a much older closure, between 13 and 23 Mya in the Early to Middle Miocene. The various dates have been proposed using three lines of evidence: geology, the fossil record, and molecular divergence times of lineages north and south (or west and east) of the isthmus. Few studies have made a link with the uplift of the northern Andes, although both geological processes are related. Here we look at this question using the basidiolichen genus Cora, which occurs in cool-temperate areas in South America as far as 40° south, while its continental boundary in Mexico is only 28° north (a difference of 1,300 km), suggesting a recent northward expansion. Since the genus diversified in the past 20 My predominantly in the northern Andes, the final uplift of the Andes between 10–5 Mya can serve as a benchmark to test the two competing hypotheses for the closure of the isthmus: either before (23–10 Mya) or after (3.7–2.8 Mya) the final Andean uplift. If an effective closure of the isthmus occurred in the Early to Middle Miocene, Cora should have migrated into Central America comparatively early, prior to its diversification in the northern Andes, with few lineages which should then have diversified north of the isthmus. If in turn the closure occurred less than 5 Mya and Cora had undergone diversification in the northern Andes by then, a comparatively larger number of lineages, mostly nested within Andean radiations, should have migrated northwards. Our data strongly support the second hypothesis: a late closure of the isthmus.