<p>The brain regions supporting spatial navigation are well studied in mammals, but their function in the spatial behavior of other vertebrates is poorly understood, especially in field conditions. Here, we measured the behavior and neural correlates of the initial stages of navigation in a territorial rainforest frog, <i>Allobates femoralis,</i> in its natural environment. Frogs were released in familiar, unfamiliar, or home areas. Only frogs released in a familiar area, but outside their home territory, showed significant orientation towards home and spent more time on elevated structures, presumably orienting in space. In contrast, frogs released back in their home territory tended to move little, whereas those released in an unfamiliar area tended to move more, possibly exploring unfamiliar sites to find familiar landmarks. Contrary to our prediction, the amphibian homolog of the hippocampus (medial pallium) did not show a selective response to the navigational task. When accounting for behavioral differences, most measured pallial and subpallial regions showed increased neural activity during frog orientation home from a familiar environment. Interestingly, despite the behavioral differences, there were few differences in brain activity between the frogs released directly back home and those released in an unfamiliar area. Overall, we find that wild poison frogs respond selectively to environmental familiarity and that most measured brain regions have more translationally-active neurons when challenged to navigate a familiar setting. Our findings support the hypothesis that, in amphibians, brain regions homologous to mammalian centers of spatial processing exhibit more task-general responses.</p>