Ascarid infections constitute clinical important endoparasitoses in captive reptiles and can cause morbidity and mortality. We describe a fatal infection in a four-year-old captive panther chameleon (Furcifer pardalis) caused by the ascarid nematode Hexametra (H.) angusticaecoides. The panther chameleon was presented with a period of inappetence and the manifestation of several threadlike subcutaneous swellings near the throat and between anterior extremities. During surgery, several nematodes were removed from the subcutaneous tissue. After re-manifestation of swellings, 26 nematodes were surgically removed in three sessions. The first coproscopic examinations of continuously sampled faeces did not reveal the presence of ascarid eggs and the first positive sample was obtained after the second surgery. In addition to the mechanical removal of nematodes, the patient was treated with Pyrantel (5 mg/kg) and 11 nematodes were found in the faeces after deworming. Infections with oxyurids and the coccidian parasites Isospora brygooi and Choleoeimeria glawi were also detected and were treated with toltrazuril and a combination of toltrazuril and clindamycin. After temporary improvement, the chameleon died one and a half months after the initial examination. Based on morphological characteristics, the nematodes were identified as H. angusticaecoides. H. angusticaecoides was also characterized molecularly. Necropsy revealed 38 nematodes in different localizations; including those isolated from subcutaneous swellings and from faeces after deworming, at least 75 (sub-)adults were found. The present report describes the pathogenesis of an H. angusticaecoides infection and discusses the aetiology and life cycle, as well as preventive and therapeutic measures.