We investigate the enamel microstructure of 37 isolated rodent incisors from several late middle Eocene and late Oligocene localities of Contamana (Loreto Department, Peruvian Amazonia), and from the early Oligocene TAR-01 locality (Shapaja, San Martín Department, Peruvian Amazonia). All incisors show an enamel internal portion with multiserial Hunter-Schreger Bands (HSB). The late middle Eocene localities of Contamana yield incisors with subtypes 1, 1–2, and 2 of multiserial HSB; TAR-01 yielded incisors with subtypes 1–2, 2, 2–3, and 3 of multiserial HSB; and the late Oligocene localities of Contamana, incisors with subtypes 1–2, 2, and 2–3 of multiserial HSB. Based on our current knowledge of the South American and African rodent fossil records and given the primitiveness of the Eocene caviomorph faunas, it may be expected that the hystricognath pioneer(s) who have colonized...