Alternative splicing is a critical mechanism for generating mRNA transcript diversity, and plays an essential role in development. Alternative splicing may also provide an efficient route for existing genes to acquire new functions, potentially driving phenotypic switching and contributing to disease such as cancer. Indeed, the splicing machinery is pathologically altered in cancer, and the degree of splicing is significantly associated with patient survival in multiple cancers, including melanoma. Recently, long-read RNA sequencing has emerged and is offering significantly enhanced sensitivity in detecting transcriptomic variation. The discovery of novel transcript isoforms by long-read sequencing is revealing the full complexity of splicing events that is previously undetected by short-read RNA sequencing approach. This allows us to explore the dynamic changes of transcript diversity in melanoma short-read RNA sequencing data by leveraging the detection of identified novel transcript isoforms. To date, a detailed analysis of alternative splicing in melanoma progression and metastasis has yet to be reported. The present study aims to address this gap by analysing alternative splicing in 110 melanoma patients using short-read RNA sequencing data from the European Genome-Phenome Archive. By generating a new transcript index from existing melanoma long-read RNA sequencing data to perform transcript assignment and quantification of short-read sequences, our analysis will explore global changes in splicing events, isoform switching, differential transcript usage, and differential gene/isoform expression across different stages of melanoma progression from primary tumours to in-transit, lymph node, and distant metastases. Understanding the changes in transcript diversity associated with melanoma progression from primary to metastatic disease may lead to new biomarkers and therapeutic approaches to stop melanoma in its tracks earlier and prevent recurrence.