Calciphylaxis is a highly morbid disease that is strongly associated with chronic kidney disease (CKD); however, the histologic criteria for diagnosis have not been well established nor have their specificity for calciphylaxis been determined. This retrospective study aimed to examine the prevalence of histologic features commonly associated with calciphylaxis in noncalciphylaxis patients. We also sought to evaluate whether these features may be more prevalent in patients with CKD. To assess this, healthy marginal skin tissue from above-the-knee amputation specimens was compared between patients with CKD (n = 23) and without CKD (n = 47). Intravascular calcification of capillaries or small-to-medium arterioles was detected on von Kossa stain in 40.0% of the entire cohort. Capillary calcification and intravascular thrombosis were more prevalent in patients with CKD. Finely stippled capillary calcification was present in 26.1% of patients with CKD versus 8.5% of patients without CKD (P = 0.0484), and intravascular thrombosis was present in 8.7% of patients with CKD and 0.0% of patients without CKD (P = 0.0403). None of the patients in this study had clinical evidence of calciphylaxis at presentation and in at least a 1-year follow-up period. This study confirms that the histologic features previously associated with calciphylaxis are nonspecific and are more prevalent in patients with CKD.