Objective The aim of this methodological paper was to present self‐contempt, and its assessment, in a broad transdiagnostic framework of psychopathology and related to change in psychotherapy. Self‐contempt may be a central phenomenon in many psychological disorders. We outline methodological recommendations for the study of complex transdiagnostic phenomena which involve multilevel biobehavioural responses. Method We illustrate the assessment of self‐contempt as a complex transdiagnostic phenomenon with a study in which emotion‐eliciting two‐chair dialogues focused on the elaboration of self‐criticism, and an observer‐rated system was applied to assess each client's expressed self‐contempt at the moment of enacted self‐criticism. The client's own self‐contemptuous words were extracted from this self‐critical dialogue and then later presented as part of a functional magnetic resonance imaging paradigm. Results This assessment paradigm was applied to a brief treatment for clients with borderline personality disorder, and the results of pre–post change over time in markers of self‐contempt are presented. Conclusions The importance of the assessment of self‐contempt in an ecologically valid manner, by using individualised stimuli and taking into account multilevel activations, is discussed in the context of a transdiagnostic conception of psychopathology and in the context of change in psychotherapy.