Here, we described a case of a 38‐year‐old Japanese woman diagnosed with anti‐centromere antibody‐positive SSc and CAPS carrying the pathogenic mutation in the NLRP3 gene, with a detailed autoantibody profile by a high‐throughput comprehensive protein array covering approximately 90% of the human transcriptome. Here, NLRP3 is linked to cryopyrin-associated periodic syndrome.