Centromere antibodies occur primarily in patients with the calcinosis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasis (CREST) syndrome variant of systemic sclerosis (scleroderma). CREST syndrome is characterized by the following clinical features: calcinosis, Raynaud phenomenon, esophageal hypomotility, sclerodactyly, and telangiectasia. Centromere antibodies were originally detected by their distinctive pattern of fine-speckled nuclear staining on cell substrates used in the fluorescent antinuclear antibody test. In subsequent studies, centromere antibodies were found to react with several centromere proteins of 18 kDa, 80 kDa, and 140 kDa named as CENP-A, CENP-B, and CENP-C, respectively. Several putative epitopes associated with these autoantigens have been described. The CENP-B antigen is believed to be the primary autoantigen and is recognized by all sera that contain centromere antibodies.