The current schizophrenia concept is built on experts’ agreement on the matter, and it is basically rooted in the epidemiological and clinical evidence. However, the numerous and intensive attempts to find the biological underpinnings of this syndrome face almost constantly a low degree of replication of the results. We have reviewed previously published work to contribute to identify some reasons underlying that failure. The difficulty in replicating biological findings in schizophrenia may relate to the intrinsic heterogeneity among patient samples, acquired through the current diagnostic criteria. As a result, the necessary replication for any finding to be accepted as characteristic data for schizophrenia would be impeded. Therefore, a new frame based on identification of correlates of the most replicated biological anomalies in schizophrenia to date may contribute to overcome those difficulties.