<b><i>Background/Aims:</i></b> The association between hidradenitis suppurativa (HS) and multiple comorbidities has been widely investigated but data about the coexistence of Down syndrome (DS) are scarce. We sought to evaluate the prevalence of DS among a population of HS patients and assess their clinical features. <b><i>Methods:</i></b> We collected demographic and clinical data of patients affected with HS referred to three Italian outpatient dermatology clinics. <b><i>Results:</i></b> A total of 257 HS patients were enrolled, 62% females and 38% males (mean age [±SD]: 23.3 ± 10.7 years); 9 of the 257 patients (3.5%), 7 females and 2 males, had concomitant HS and DS. The patients with DS and HS had a significantly earlier age of onset (mean age: 14.3 ± 3.6 vs. 23.4 ± 12.31 years; <i>p</i> = 0.029), a significantly younger age at diagnosis (mean age: 21.1 ± 11.1 vs. 31.8 ± 13.5 years; <i>p</i> = 0.015), and were significantly younger (mean age: 23.3 ± 10.7 vs. 34.6 ± 13.07 years; <i>p</i> = 0.005). No significant differences about other clinical data were found between the two groups.<b><i> Conclusion:</i></b> The prevalence of DS in HS patients corresponds to a not negligible 3.5% of cases, who experienced an onset of HS at a younger age compared to patients with HS only.