In recent years, the multiple-reader, multiple-case (MRMC) study paradigm has become widespread for receiver operating characteristic (ROC) assessment of systems for diagnostic imaging and computer-aided diagnosis. We review how MRMC data can be analyzed in terms of the multiple components of the variance (case, reader, interactions) observed in those studies. Such information is useful for the design of pivotal studies from results of a pilot study and also for studying the effects of reader training. Recently, several of the present authors have demonstrated methods to generalize the analysis of multiple variance components to the case where unaided readers of diagnostic images are compared with readers who receive the benefit of a computer assist (CAD). For this case it is necessary to model the possibility that several of the components of variance might be reduced when readers incorporate the computer assist, compared to the unaided reading condition. We review results of this kind of analysis on three previously published MRMC studies, two of which were applications of CAD to diagnostic mammography and one was an application of CAD to screening mammography. The results for the three cases are seen to differ, depending on the reader population sampled and the task of interest. Thus, it is not possible to generalize a particular analysis of variance components beyond the tasks and populations actually investigated.