The term aplasia cutis congenita characterizes a heterogeneous group of diseases which have in common a focal absence of the skin. The defect may be limited to the epidermis but often involves the full thickness of the skin including the underlying bone. At birth the lesions present as erosive patches and they heal rather rapidly with a residual scar. Although more than 200 publications on aplasia cutis congenita have appeared in the medical literature between 1966 and 1999, surprisingly no case of malignant degeneration has been described. We observed a 58-year-old male patient with aplasia cutis congenita who developed crusted changes within the scar over the past 10 years. Repeated biopsies over the years have always documented a precancerous lesion without solar elastosis. Invasion has never been observed in this patient. We hypothesize that for invasive malignancies dermal-epidermal interactions are necessary. Such a cell to cell communication seems to be impossible in patients with aplasia cutis congenita, as the dermal-epidermal unit is not developed. Aplasia cutis congenita might serve as an interesting model for further investigations on the importance of epidermal-dermal interactions.