The aim of the study was to test MYO9B gene polymorphisms for association with three autoimmune diseases, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and celiac disease (CD), in a Spanish population. We analyzed three SNPs (rs2305767, rs1457092, and rs2305764) in a case-control cohort composed of 349 SLE patients, 356 RA patients, 90 CD patients, and 345 healthy controls. All three SNPs showed a consistent increased frequency of the A allele in SLE, RA, and CD patients compared with healthy controls. An association was observed between CD and rs2305764 (p=0.01, OR=2.3), between SLE and rs1457092 (p=0.002, OR=1.4), and between RA and rs1457092 (p=0.02, OR=1.3). The three autoimmune diseases combined showed significant association with rs1457092 and rs2305764 and with the AAA haplotype (p haplotype=0.005, OR=1.3). Our data demonstrate consistent association with the A allele and AAA haplotype of three SNPs in the MYO9B gene, which were previously reported to be associated with CD in the Dutch population. This suggests that genetic variation in MYO9B is associated with CD, SLE, and RA and that MYO9B is a general risk factor for autoimmunity.