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Abstract: Mastocytosis is a primary, abnormal accumulation of mast cells associated with a broad range of local and systemic symptoms. We report two female adolescents with episodic, unilateral, swelling of the labia majora that was discovered to be an unusual presentation of mastocytosis. Mastocytosis is frequently misdiagnosed because of its rarity and variable clinical presentation, which often mimics other conditions. In the appropriate setting, mastocytosis should be included in the differential diagnosis of labium majus swelling.