To stratify adult-onset Still's disease (AOSD) patients in distinct clinical subsets to be differently managed, by using a multi-dimensional characterisation.AOSD patients were evaluated by using a hierarchical unsupervised cluster analysis comprising age, laboratory markers systemic score, and outcomes. The squared Euclidean distances between each pair of patients were calculated and put into a distance matrix, which served as the input clustering algorithm. Derived clusters were descriptively analysed for any possible difference.Four AOSD patients clusters have been identified. Disease onset in cluster 1 was characterised by fever (100%), skin rash (92%), and arthritis (83%) with the highest ferritin levels (14724 ± 6837 ng/ml). In cluster 2 the onset was characterised by fever (100%), arthritis (100%), and liver involvement (90%) together with the highest CRP levels (288.10 ± 46.01 mg/l). The patients in cluster 3 presented with fever (100%), myalgia (96%), and sore throat (92%). The highest systemic score values (8.88 ± 1.70) and the highest mortality rate (54.2%) defined cluster 3. Fever (100%) and arthritis (90%) were the symptoms at the onset in cluster 4, which was characterized by the lowest ferritin and CRP levels (1457 ± 1298 ng/ml; 54.98 ± 48.67 mg/l).Four distinct phenotypic subgroups in AOSD could be suggested possibly associated with different genetic background and pathogenic mechanisms. Our results could provide the basis for a precision medicine approach in AOSD, trying to find a clinical and laboratory multidimensional stratification and characterisation, which would drive a tailored therapeutic approach in these patients.