This report describes the morphologic, ultrastructural, and immunophenotypic features of a nodular ganglioneuroblastoma in the jejunum of a 13-month-old Holstein-Friesian heifer. On histologic examination, the mass was composed of clusters of neuroblasts and isolated ganglionic neurons in abundant neurophilic matrix that was surrounded by scanty Schwannian stroma. On ultrastructure examination, the large ganglionic neuron-like cells had unmyelinated neurites. Most ganglionic neuron-like tumor cells expressed neurofilament, neuron-specific enolase, chromogranin A, and S-100, whereas the Schwann-cell-like stromal cells expressed S-100 and vimentin. Both brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase-B (Trk-B) were expressed in ganglionic neuron-like tumor cells, which suggested the activation or reactivation of an embryonic autocrine BDNF/Trk-B pathway that could have prolonged cell survival and promoted differentiation with neurite formation.