Abstract: Histiocytes play an important role in defense mechanism (innate and acquired immunity) by phagocytizing pathogens and / or cellular debris and by presenting antigens to stimulate lymphocytes and other immune cells to augment response to pathogens. Abnormal proliferation of histiocytes occur in cell differentiation and results in histiocytic sarcoma (HS). It is extremely rare and malignant form of tumor with usually aggressive clinical course. The signs and symptoms are systemic symptoms (fever, weight loss), hepatosplenomegaly, adenopathy’s, intestinal obstruction, rash and pancytopenia. Here, a case report on 12- year- old female patient suffering from histiocytic sarcoma for 1 year 10 months. A relief in form of decrease in size of lump present at neck and relief in systemic symptoms were noted by treatment of one month of Ayurvedic medicine and local application of Lepa, which clearly indicate the efficacy of Ayurveda treatment and improve quality of life of patient.