OBJECTIVES: Little data are available on the burden of ASM, a subtype of systemic mastocytosis (SM) and severe form of mast cell disease that may progress to mast cell leukemia. This study reviewed the literature in order to estimate the burden of ASM in the US. METHODS: A systematic literature review was conducted to identify publications from 2000-2011; 181 citations were identified and 6 articles abstracted. The US population-level burden of ASM was estimated using an Excel model. Direct treatment costs were calculated from treatment patterns described in identified publications. RESULTS: ASM involves multiple organ systems, resulting in potentially severe symptoms/conditions including anaphylaxis/allergic reactions, osteoporosis, hepatomegaly, splenomegaly, gastrointestinal symptoms, fatigue, and weight loss. There is no known cure for ASM. Median survival was 41 months in a published cohort study. No publications were identified providing US epidemiology data. Two estimates were calculated for the prevalence of ASM in the US in 2010: 616 and 1,220. A global prevalence rate of 0.2/100,000 resulted in 616 cases. An SM prevalence rate of 3.3/100,000 (assuming 12% ASM) resulted in 1,220 cases. Incidence was estimated at 111 cases in 2010 using an SM incidence rate of 0.3/100,000 (assuming 12% ASM). The proportion of ASM/SM cases ranged from 7-18% in the literature with 12% from the largest study. No studies were identified examining the economic burden of ASM. In this model, direct monthly per-patient costs were estimated between $5232 and $8741. These are likely underestimated as a result of limited resource utilization information in the literature. CONCLUSIONS: These results provide preliminary estimates for the burden of ASM in the UNITED STATES. Additional research can assist in further quantifying these estimates. In addition, it is likely that ASM patients experience tremendous indirect costs due to the symptomatic burden of the disease and further evaluation is warranted.