Abstract Introduction Medical students are often unaware of the relationship between mood/anxiety disorders and cardiovascular disease (e.g., the behavioral and biological mechanisms through which depression might lead to, or exacerbate coronary artery disease). To improve both the assessment and management of such patients we created this problem-based learning (PBL) case. Methods Like most PBLs, this case has two parts. Part 1 involves a case introduction, where facilitators help students discuss the case, develop learning objectives, and choose which objectives to work on before the next session. Part 2 involves the resolution of the case where students present the results of their independent research on the learning objectives. When administering this PBL, facilitator training is essential. A 1-hour session covering PBL process in general and the specific content of this case should be sufficient. It is useful to have faculty from both psychiatry and internal medicine present during both training and the actual PBL. The case can easily be adapted for use in either clinical or preclinical experiences and in different specialty courses. Results In terms of effectiveness, medical student response was assessed after running this PBL for 1 year. Nearly 40% of participating students found that the PBL contributed a “significant” or “considerable” amount to their overall learning; over three-fourths found it at least moderately helpful in this regard. Faculty facilitators consistently noted how effective this PBL was in generating student interest and discussion. Qualitative review of student presentations related to PBL learning objectives showed effective knowledge retrieval/acquisition and higher-level analysis, superior to other PBLs used previously in the psychiatry course. Discussion The significance of this PBL, lies in the approach to teaching comorbidity-sharing conditions among specialties. This challenges students to think outside of traditional silos, and reinforces the importance of an extremely common yet undertaught clinical situation. The learning objectives listed could easily be changed to meet the needs of a particular course or clerkship; in fact, the PBL process itself encourages students to develop their own learning objectives independently, so there would likely be some differences between what students choose to focus on compared to what we have listed.