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The vast majority of tumours in the sellar region are pituitary neuroendocrine tumours, also called pituitary adenomas. Sellar gangliocytomas (GCs), benign tumours that originate from neuronal ganglionic cells, account for less than 1% of sellar tumours. Even rarer are mixed gangliocytoma-pituitary neuroendocrine tumours (GC-PitNET). These tumours are often associated with hormone hypersecretion, most commonly resulting in acromegaly. The histogenesis of mixed GC-PitNET is currently unclear. In this paper, we present comprehensive clinical, immunohistochemical, targeting enrichment next generation DNA sequencing, and genome-wide methylation data from four patients with mixed GC-PitNETs, three with acromegaly and one with Cushing's disease. Transcriptomic data are also included for two of the patients. Our findings indicate that mixed GC-PitNETs have different clinical course, with the acromegaly patients showing greater resistance to pharmacological therapy, as well as different protein expression and molecular features compared to respective pure PitNETs. The transcriptomic data on two patients with somatotroph GC-PitNET show involvement of mitochondrial and ribosomal genes, suggesting a distinct gene expression pattern, in comparison with pure somatotroph tumours. Furthermore, the expression pattern of selected stem cell markers, mainly SOX9, supports a common origin of the neuroendocrine and ganglionic tumour components, suggesting the involvement of stem cells in tumorigenesis.