Mastocytosis denotes a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells. Cutaneous mastocytosis is characterized by skin-limited disease and is the most common subtype. Systemic mastocytosis has extracutaneous organ involvement with variable symptomatology and prognosis. Clinical manifestations are secondary to mediator release or direct organ infiltration of mast cells. Current available treatment for systemic mastocytosis is non-curative with conventional symptom-directed therapy for all subtypes. Cytoreductive agents are available for those with refractory symptoms or extensive extracutaneous disease. To date, clinical responses remain mixed and systemic mastocytosis is still an incurable condition.