Background This article introduces a new treatment protocol for depression. Based on previous research which indicated the presence of cognitive conflicts in depression, this study created an intervention manual to address these conflicts. Method The therapy manual for depressive patients followed the guideline for inclusion in clinical trials (stage II), which has received high recognition. A preliminary version (stage I) of this manual was formulated based on other, more general dilemma-focused therapy publications, inspired by personal construct theory (PCT), and input from clinical experience. The resulting version was then applied during the 8-session format of a pilot study with patients diagnosed with major depressive disorder or dysthymia. Finally, feedback was requested from seasoned and highly respected therapists, some of whom were familiar with PCT. Results According to the mentioned guideline, the intervention manual selected the theoretical framework, in this case PCT, to include its conceptualization of depression and resolution of dilemmas (to foster clinical improvement) as a main treatment goal. The manual was then contrasted with psychoanalytic psychotherapy, cognitive-behavior therapy (CBT), motivational interviewing (MI), and other similar approaches such as cognitive-analytic therapy and coherence therapy. Following these conceptual clarifications, the specific interventions included in the manual were defined according to both categories: their unique and essential components and those conceived as common psychotherapeutic factors. Next, the general structure and content for each session were presented. The structure consisted of seven well-defined individual sessions with an additional session, which could complement any of the former sessions to address the patient's issues in greater depth, if needed. Conclusions This Dilemma-Focused Intervention manual aimed to improve the treatment outcome for depression by offering an intervention that could be combined with other general approaches. At its present level of definition, it allows for inclusion in controlled trials (eg, the current RCT combining group CBT with this intervention). Thus, this manual added to the existing resources in psychotherapeutic research and practice for treatment of depression.