Calreticulin 3 (CALR3) is considered a candidate gene in human male infertility because male, but not female, CALR3-deficient mice are infertile. To investigate the possible association between variations in CALR3 and impaired spermatogenesis in humans, we screened for mutations in human CALR3 using DNA from 892 infertile male patients and 167 proven-fertile male volunteers. The frequent appearance of several single nucleotide polymorphisms (SNPs), including 742G>T (Asp248Tyr), 976G>A (Asp326Asn), and 1058A>T (Lys353Met), were found in the infertile group by direct sequencing of amplified fragments using the same primers as for polymerase chain reaction. Our results indicate that three major SNPs associated with male infertility exist in the open reading frame of CALR3.