Ocular melanoma is a rare but clinically significant malignancy, primarily comprising uveal and conjunctival subtypes. Although sharing some histopathological features with cutaneous melanoma, these tumours are characterized by distinct molecular and biological profiles with direct implications for prognosis and treatment. Uveal melanoma is predominantly driven by mutations in GNAQ and GNA11, along with alterations in BAP1, SF3B1, and EIF1AX, which are key prognostic determinants. Conversely, conjunctival and eyelid melanoma exhibits greater molecular similarity to cutaneous melanoma, commonly involving BRAF, NRAS, NF1, and TERT promoter mutations. Despite progress in the molecular characterization of these entities, metastatic disease continues to confer a poor prognosis, particularly in uveal melanoma. Ongoing research into the molecular basis of ocular melanoma is essential to advance targeted therapies and improve clinical outcomes. The aim of this review is to provide a comprehensive overview of ocular melanoma, with a particular focus on the molecular biology underlying its clinical behaviour and emerging therapeutic opportunities.

Methylthioadenosine phosphorylase (MTAP) loss is an emerging biomarker in several human malignancies, mainly due to its frequent co-deletion with CDKN2A on chromosome 9p21. Beyond its diagnostic value, MTAP deficiency has important biological consequences, including metabolic reprogramming, immune microenvironment modulation, and increased dependency on PRMT5-related pathways. This review summarizes the current evidence on MTAP alterations across different tumor types. The role of MTAP immunohistochemistry as a practical surrogate for CDKN2A homozygous deletion is discussed, together with its advantages and interpretative limitations. In addition, the potential predictive relevance of MTAP loss for immunotherapy, antifolate-based treatments, and novel PRMT5-targeted strategies is explored. Overall, MTAP assessment represents a promising tool in modern diagnostic pathology and precision oncology, bridging morphology, molecular alterations, and therapeutic decision-making.