The identification of KIT D816V mutation as a key driver for the expansion and accumulation of neoplastic mast cells in systemic mastocytosis (SM) has significantly improved the diagnosis, subclassification, and management of SM. Moreover, the advent of novel targeted therapies has dramatically changed the treatment landscape. However, challenges persist for community clinicians due to the low prevalence of SM and its vague and wide spectrum of clinical features. Expanded knowledge of the recommended pathology and laboratory evaluation for the diagnosis and subclassification of the disease is needed to shorten delays in diagnosis and delivery of optimal care. Tune in and find out more about the management of SM and the latest clinical evidence and guideline recommendations for the use of tyrosine kinase inhibitors (TKIs) and learn about the role played by pathologists in the identification and diagnosis of SM, which ultimately guides treatment selection.