Introduction: Ganglion cells of the hypoglossal nerve (HN) have been confirmed in certain animals but have been thought not to be present in man. To investigate for the presence of these structures in adult humans and if present, to verify their functionality, the present study was performed. Materials and Methods: We harvested adult cadaveric HN and observed for ganglion cells. Histological and immunohistochemical analyses were performed on all specimens. Results: Ganglion cells were found in 33% of specimens. Using immunohistochemistry, we found that these ganglia were sympathetic in nature. Based on our findings, ganglion cells do exist in the human HN although they are located sporadically and are found inconstantly. Conclusions: Such information may be valuable in elucidating other functions of the HN and may aid in the histological diagnosis of this nerve. Additionally, pathology involving HN such as paragangliomas, are supported by our findings of the presence of autonomic ganglion cells in some HN specimens. © Springer-Verlag 2008.