Most melanocytic tumours carry driver mutations such as BRAF, NRAS or NF1, and a subset are driven by gene rearrangements involving genes like BRAF, ALK, ROS1, NTRK1/2/3, MAP3K8 and PRKCA, several of which are characteristically associated with Spitz neoplasms. The rise of molecular immunohistochemistry and highly sensitive DNA and RNA-based next-generation sequencing has improved variant detection, but can produce false positive and false negative results that can confuse diagnosis. The talk will summarise the journey of a few recent challenging cases.