Background: Acquired perforating dermatosis (APD) comprises an uncommon group of skin disorders that develop in adulthood in association with systemic diseases. The aim of this study was to characterize clinicopathologic features and treatment outcomes in a series of patients diagnosed with APD. Methods: Retrospective study of all patients diagnosed with an APD over a 10‐year period (2009–2018) at a tertiary teaching hospital in Lisbon, Portugal. Results: Fifty‐seven patients with APD were identified. Thirty‐five patients presented lesions in multiple anatomic areas (61.4%), and the lower limbs were the most common location. Forty‐six patients reported pruritus (80.7%), which was classified as severe in 21 of them (36.8%). An underlying systemic disease was identified in 53 patients (93.0%). Diabetes mellitus (DM) and chronic kidney disease (CKD) were the most common associated systemic diseases, but psychiatric disorders, malignancies, and chronic infections were present in a significant number of patients. The combination of topical steroids with antihistamines was the most prescribed initial treatment, but only 37.8% of the patients had a complete response. Acitretin, systemic steroids, and phototherapy were the treatments associated with the best outcome. Conclusion: Acquired perforating dermatosis can be associated with many systemic disorders that have pruritus as a common factor. Chronic viral infections and an occult malignancy should be sought, particularly in the absence of DM and CKD. The management of APD is challenging and is best achieved with the control of the underlying systemic diseases. [ABSTRACT FROM AUTHOR]