A 35-year-old female presented in 1989 with hepatosplenomegaly, but no conclusive diagnosis was established. From 1992, she experienced transient episodes of facial flushing and palpitations. Osteosclerotic change was detected radiologically. Colonoscopy revealed massive polypoid lesions. Mast cells were demonstrated in bone marrow smear and imprinted preparations of colon biopsy specimens by toluidine blue staining. Plasma concentrations of histamine and soluble c-kit were elevated. She was successfully treated with interferon-alpha and prednisolone, resulting in the disappearance of histamine-related attacks and a gradual decrease in tumor size. However, the remission was interferon dose dependent. This case was considered as systemic mastocytosis with massive polypoid colon lesions and showed the importance of maintenance therapy with interferon-alpha.