In the present study, cytological properties of bone marrow mast cells (MC) were analyzed and correlated with clinical parameters in 69 patients with systemic mastocytosis (SM). Based on cytomorphological features, four distinct cell types were recorded: (i) typical tissue MC (round cells, well granulated, round central nuclei); (ii) atypical MC exhibiting elongated cytoplasmic extensions, oval nuclei with excentric position, and a hypogranulated cytoplasm with focal granule accumulation ('atypical MC type I'); (iii) atypical MC with bi- or multilobed nuclei ('atypical MC type II'); and (iv) metachromatically granulated blast-like cells. In the majority of cases with SM, the percentage of MC in bone marrow (bm) smears was less than 5% (of all nucleated bm cells), and the predominant types were typical MC or atypical MC type I. In a smaller group of patients, the percentage of MC was greater than 5% and a significant subset of MC (>or=10%) were classified as 'metachromatic blasts' and/or atypical MC type II. These patients had a significantly shorter survival (P<0.05) and most of them were found to lack UP-like skin lesions. A percentage of MC>or=20% was invariably associated with the diagnosis 'mast cell leukemia'. Multivariate analysis confirmed the prognostic value of the cytology in SM and identified the percentage of MC (of all nucleated bm cells) as an independent prognostic variable. These data suggest that cytomorphological assessment of bm MC in SM is an important diagnostic approach that may help to delineate between variants of the disease.