Kyrle's disease is an uncommon form of acquired transepidermal elimination dermatosis frequently associated with diabetes mellitus and chronic kidney disease. An association with malignancy has been sporadically reported in the literature. Here, we describe the clinical course of a diabetic patient with end-stage renal disease who developed this disorder as a herald to a regionally advanced renal cell carcinoma. We provide a focused literature review and rationale for the definitive categorization of acquired perforating dermatosis as a potential paraneoplastic manifestation of systemic malignancies. Clinicopathological correlation and prompt communication among clinicians for occult malignancies are always warranted. Furthermore, we describe a novel association of one of the subtypes of acquired perforating dermatosis with such malignancies.