The precise pathogenesis of the ascending aortic aneurysm (AscAA) remains to be determined. Mast cells in the adventitia of human AscAA lesions may play a role in this pathogenesis. Adventitial mast cell density per 10 high-power fields (0.25 mm(2)) was assessed in multiple biopsy samples, from aneurysmal aortic sections (n = 41) and control (nondilated) aortic specimens (n = 50), stained by orcein-Giemsa method, an inexpensive (<$1) method. In a multivariable adjusted logistic regression model, using AscAA as the dependent variable, mast cell density was found to be an independent predictor of AscAA occurrence (odds ratio = 2.21; 95% confidence interval = 1.58-3.08; P < .001). Receiver operating characteristic curve analysis showed that the proposed cutoff value of ≥ 3 mast cells per 10 high-power fields was very sensitive to detect AscAA occurrence, yielding a sensitivity of 90% with a specificity of 80%. In conclusion, a significant increase in the number of mast cells in the adventitia of human ascending aortic lesions proposes a role for these cells in the pathogenesis of AscAA.