The Atlantic bluefin tuna (Thunnus thynnus) is an extraordinary fish that has amazed humanity since ancient times. However, the continuous overexploitation of this fishery, particularly in the Mediterranean Sea, could result in a total collapse of this resource. Currently, this species is managed as two stocks: Western Atlantic and Mediterranean-Eastern Atlantic, with a recognized genetic differentiation between them. On the other hand, the population structure within the Mediterranean Sea is still unclear. The biological data supports the idea of two separate populations in the eastern and western Mediterranean basins. However, nuclear microsatellite and mitochondrial DNA (mtDNA) analyses of two samples representative of these two basins result in a lack of heterogeneity. A comparison of these results with previously published studies reveals some discrepancies. We have compared 59 genetic differentiation tests that include samples within the Mediterranean. Of these, about 60% gave significant differentiation while the remaining 40% were non-significant. But, when only nuclear-based loci were considered, genetic differentiation was detected in up to 73% of the cases with an average significant F (ST) of only 0.018, whereas the average significant F (ST) of the mtDNA-based studies was significantly higher (0.029). However, in some cases, it is difficult to reconcile the biology of the species with the results suggesting genetic differentiation. In conclusion, although it is not yet possible to reach a definitive conclusion about the population structure, but considering all biological and genetic data, we suggest an independent management approach for each basin to avoid the impact of a type II error that could lead to the possible loss of the regional subpopulations.