AdCC is predominantly driven by the activation of the proto-oncogene MYB which encodes a transcription factor that in turns governs cell fate and stem-progenitor cell expansion; key processes subverted in cancer. The development of 3D models of AdCC has provided an unprecedented opportunity to explore a novel link between MYB expression and a neural crest cell fate marker expression. Consistent with the neural crest cell of origin of this tumour we examined this relationship by profiling of tumouroid cultures for MYB and neuronal and stem cell gene expression signatures (eg, SOX10, CD133, Nestin, NOTCH1, MAP2, GMP6b, FAB7, TUBB3). In parallel we have undertaken a comprehensive multiplex immunohistochemistry analysis of tumouroids of these gene markers. In rarer situations, AdCC is driven by a MYB family member – MYBL1 (A-MYB) and here we explored the reciprocal situation where either but both family members are expressed. This information is highly relevant to understanding outcomes of reported and ongoing AdCC clinical trials that target MYB.