Hematological neoplasms associated with systemic mast cell disease are most frequently of myeloid origin. There are a few reports, however, of systemic mastocytosis (SM) cases associated with lymphoid or plasma cell neoplasms as well. In this report, the authors present a case of SM (with D816V mutation in the c-KIT gene) associated with JAK2 V617F mutation negative essential thrombocythemia. The leading symptom of the 78-year-old female was recurring hydrothorax that responded only to interferon alpha therapy. During the first year of therapy, the patient developed insulin-dependent diabetes and hypothyroidism. The hematological workup also revealed IgG kappa monoclonal gammopathy that was non-progressive in the following next three years. Low levels of complements without known clinical significance accompanied the entire picture.