Sphiggurus vestitus pruinosus, a porcupine from western Venezuela, has a karyotype with a diploid number (2n) of 42, and a fundamental number (FN) of 76. The autosomes consist of 34 metacentric and submetacentric, 2 subacrocentric, and 4 acrocentric chromosomes. The X‐chromosome is submetacentric, and the Y‐chromosome is acrocentric. This karyotype is identical in gross morphology to that of the North American porcupine,Erethizon dorsatum, but differs markedly from the 2n=74 and FN=82 karyotype of the Panamanian porcupine,Coendou rothschildi. These findings are unexpected considering thatSphiggurusandCoendouresemble morphologically more to each other than either of them toErethizon, and are most parsimoniously explained by retaining the hypothesis of a closer cladistic relationship betweenSphiggurusandCoendouand by proposing the 2n‐74 and FN=82 karyotype to be autapomorphic. The karyological information is complemented with observations on cranial and external characters. The results support recognition ofSphiggurusandCoendouas separate genera.