Chronic histaminergic angioedema (CHA) may be classified as a separate acquired angioedema (AE) or as an endotype of chronic spontaneous urticaria (CSU). Arecent study suggested them to be independent pathologies. We carried out an exhaustive analysis between CHA and AE-CSU to explore the possible differentiation between them on the bases of a series of predictors. An observational, retrospective, cross-sectional, and exploratory study was designed. Fifty-six CHA and 40 AE-CSU patients were included. Data were extracted from the year before and year after time of diagnosis. Apredictive model was generated by logistic regression, and its discriminatory power was assessed using the area under the receiver operating characteristic curve. The average frequency of AE attacks per year turned out to be higher in the AE-CSU group than in the CHA group, both before (median [interquartile range] 12 [43] vs 8 [16]) and after (24.3 [51.2] vs 2 [4.25]) diagnosis, respectively. The uvula was more frequently affected in CHA. No other differences were found. However, using 7 clinical characteristics of the patients, a multiple logistic regression model was able to predict, with a specificity of 86.4%, a sensitivity of 92.3%, and an area under the curve of 95.1% (P= .024), that CHA and AE-CSU behaved differently. CHA has similar characteristics to AE-CSU, although they slightly differed in the frequency of attacks andtheir location. Despite its similarities, a multiple logistic regression model that used clinical and evolutionary characteristics allowed the differentiation of both pathologiesand supports the idea that these 2 entities are independent.