The Great Barrier Reef (GBR) is one of the few remaining Pacific reef systems where the giant clam, Tridacna gigas, can be found in large numbers. Genetic data from Inter-Simple Sequence Repeat loci (ISSR) suggest low levels of genetic structuring among four north-central GBR populations (PhiPT = 0.0322, p = 0.005), with significant genetic differences evident between populations from Thetford and Grub Reefs. The data suggests a weak correlation of genetic differentiation among populations and their linear distance of geographical separation. The region of the GBR sampled here is approximately a quarter of the total distribution of T. gigas. Significant genetic structuring may therefore be present between northern and southern GBR T. gigas populations and consequently, a conservative approach should be practiced relating to the translocation of this species throughout the GBR.