Acquired perforating dermatosis (APD) is an uncommon skin disease characterized by umbilicated hyperkeratotic lesions, and involves the transepidermal elimination of dermal components, including collagen and elastic fibers. The disease can affect patients with systemic disorders, especially those with chronic renal failure or diabetes mellitus. The current paper described four cases of patients with APD and investigated the clinical characteristics and prognosis of APD, as well as its possible link with systemic disorders. In each of the four cases, the patient had systemic disorders before the onset of APD, three had concomitant renal and thyroid disorders and one had hepatocirrhosis secondary to chronic hepatitis C. The results of the present study showed that APD occurred after the transient worsening of the original systemic disease. Furthermore, it was revealed that dermatosis symptoms were alleviated upon remission of the original systemic disorder, without specific dermatological treatment. Dermatosis symptoms improved in all four patients, indicating that the management of the associated systematic diseases was essential for the successful clinical outcomes of APD.