A new species of Neotropical rodent of the genus Aepeomys is described based on 24 specimens collected in the Andean region of Venezuela (Lara and Trujillo States). Among the diagnostic characters are: large size; first and fifth digits of pes not extending beyond the commissure of digits 2-3 and the first interphalangeal of digit four, respectively; posterior margin of zygomatic ramus of the maxilla with a distinctive notch; palate extending to the posterior border of M3 or behind this molar; and paraflexus of M1 and M2 divided by an enamel bridge. In addition, the new species shows the following karyological features: 22 chromosomal pairs (2n = 44); 46 autosomal arms (FN = 46); a low proportion of two-armed elements; automosal chromosomes with abundant heterochromatin around the pericentromeric areas; and short arms of chromosomes X and Y entirely heterochromatic. According to the most recent systematic revision of the species assigned to Aepeomys, only two forms could be considered as members of this genus: A. lugens (the type species) and the taxon described herein. Both have geographic distributions restricted to highlands from the northern Andes, where the new species inhabits primary cloud forests and páramos located in the northeastern extreme of the Venezuelan Andean Cordillera. © Urban & Fischer Verlag.