When individuals have higher evolutionary fitness because of being heterozygous at a given gene region, it is known as overdominance. Although overdominant selection could represent an important mechanism for maintaining genetic variation within species, the prevalence of this mode of selection appears to be relatively low. Identification of cases of true single-locus heterozygote advantage are thus useful reference points in our overall understanding of how various forms of balancing selection influence and maintain genetic variation in natural populations. Here we report the apparent long-term maintenance of diversity via overdominant selection with homozygous lethality at an elongation factor locus in the sea star Pisaster ochraceus. Observing this pattern in a gene with such major effects on protein assembly indicates that overdominant selection could be a more prevalent factor in maintaining allelic diversity in the wild than previously recognized.