Putting together the results obtained with microarrays, we may conclude that sensitivity and specificity are similar, if not better, than conventional methods. However, some points deserve further work: a) assay standardization represents a major concern. Moving from research platforms and methods to techniques available for day-to-day practice implies a careful evaluation and validation of analytical performances, particularly precision and bias. From an analytical standpoint, a number of spotted autoantigens, such as certain Sm and histone proteins, are not always detectable with planar assays, possibly due to loss of three-dimensional structures, steric interference and/or electrostatic repulsion. Such issues have to be solved, and standardization processes, internal quality control and external quality assessment programs are required; b) interpretation of autoantibodies profiles requires competence and the establishment of common standards for the publication and sharing of microarray-generated data is mandatory; c) some ethical problems may derive from the utilization of autoantibody profiling in clinical practice, namely the presence of unexpected and unrequested auto-antibodies, when an extended profile is used. This is particularly relevant if the autoantibody finding is unexpected in the light of the initial clinical suspicion. The flexibility of the diagnostic system and the composition of the profiles acquire great importance but, even more important, is the laboratory-clinical interface, and in particular a consensual agreement between laboratorians and clinicians on the possible reporting of unrequested autoantibody specificities, if positives.