The disease extent of mastocytosis can be assessed by measurement of mediators or their metabolites, secreted from mast cells. In the present study, we compared results of urinary N-methylhistamine measurements with analysis of total tryptase in serum from patients with suspected mastocytosis.Tryptase in serum was determined with the UniCAP tryptase fluor-enzyme-immunoassay, according to the manufacturers' instructions (Pharmacia, Woerden, Netherlands). N-methylhistamine in urine was determined by competitive radioimmunoassay, according to the manufacturers' instructions (Pharmacia).A significant correlation between serum tryptase and urine N-methylhistamine was found both for 138 patients aged 14 or older (Spearman Rank r s =0.43, p<0.0001) and for 23 younger patients (Spearman Rank r s =0.46, p=0.0267). The between-run coefficient of variation of the tryptase assay was half (6.7%) of the one (13%) found with the urinary N-methylhistamine assay. Both for urine N-methylhistamine and serum tryptase, a significant difference was found between corresponding biopsies with an increased number of mast cell aggregates and biopsies without such an increase. The difference between tryptase levels however was stronger (Mann–Whitney: p=0.0012) than the difference between N-methylhistamine levels (Mann–Whitney: p=0.0140).Serum tryptase discriminates better than urinary N-methylhistamine between patients with an increased number of mast cell aggregates and persons without such an increase.