Background: Calciphylaxis is a rare, life-threatening disorder associated with chronic renal failure, presenting with ulcerating plaques leading to death by sepsis in 60% of patients. Calcification of subcutaneous arterioles, thromboses, and extravascular calcification have been demonstrated in incisional biopsy specimens. However, the sequence of these pathologic events is unknown. Objective: We examined a calciphylaxis plaque to document the wave of pathologic change from its center to its periphery. Methods: A calciphylaxis plaque was excised postmortem from a female patient. It was examined histologically along 12 radii from the center of the lesion to its periphery. Results: Calcification of small subcutaneous vessels was present in all histologically abnormal sections and extended further peripherally than extravascular calcification by up to 3.0 cm and further than subcutaneous thrombosis by up to 1.5 cm. Conclusion: Vascular mural calcification is an early and essential process in the development of a calciphylaxis plaque. (J Am Acad Dermatol 2002;47:53-7.)