Reduced bone mass with or without fragility fractures is a common feature of mastocytosis, particularly in adult males. However, bone mineral density does not account for all the fragility fractures, being a part of them attributable to impairment in bone quality. Aim of this study is to assess the usefulness of DXA-derived geometry and structural indexes in the assessment of bone status in mastocytosis. Ninety-six consecutive patients (46 women and 50 men) affected by cutaneous (CM) or systemic (SM) mastocytosis were studied. Mean age (± SD) was 53.3 ± 14.23. Spine lateral X-rays for Genant's scale, DXA for lumbar (L) and femoral (F) bone mineral density (BMD), bone strain index (BSI), lumbar trabecular bone score (TBS), and hip structural analysis (HSA) were performed. Among the laboratory variables, data of serum tryptase were reported. Tryptase was higher in SM (p = 0.035), inversely correlated with LBMD (r = − 0.232;​ p = 0.022) and TBS (r = − 0.280;​ p = 0.005), and directly with L-BSI (r = 0.276;​ p = 0.006). L-BSI remained statistically significant (p = 0.006;​ adjusted R2 = 0.101) together with mastocytosis (SM or CM:​ p = 0.034) in the multivariate regression model with tryptase as dependent variable, being LBMD and TBS not statistically significant (p = 0.887, and p = 0.245, respectively). Tryptase increased about 22 units for each unit increase of L-BSI and about 18 units for SM against CM. L-BSI was lower (p = 0.012), while FN-BSI and FT-BSI were higher in women (p < 0.001) than in men. HSA indexes were significantly higher in men, particularly with SM. SM is a risk factor for reduced bone mass, texture and strength. Since mean L-BSI and Z-modulus of all the femoral sites are statistically higher in men than in female, it could be argued that men have a better femoral bone resistance to bending forces than women, but a worse lumbar bone resistance to compressive loads. DXA indexes of bone quality are useful in mastocytosis’ bone assessment and its clinical management.