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Background: Takotsubo syndrome (TTS) is an acute heart failure syndrome characterized by transient left ventricular dysfunction, increased myocardial biomarkers, and electrocardiographic changes. Symptoms of TTS are similar to those of acute coronary syndromes, but there is often no significant coronary stenosis. Although emotional and physical stressors are often reported as having triggered TTS, the pathogenesis is largely unknown. To address this issue, we comprehensively characterized a monozygous pair of twin sisters, one of whom experienced TTS. Case summary: The 60-year-old Caucasian monozygotic female twins with and without TTS were examined at the University Hospital Zurich in Switzerland. The twins completed questionnaires and clinical interviews assessing several sociopsychological factors. The twin sister with TTS exhibited higher levels of anxiety, vital exhaustion, social inhibition, and alexithymia, and lower levels of quality of and meaning in life. She was given the diagnoses of social phobia, adjustment disorder, specific anxiety disorder, obsessive-compulsive personality disorder, and an accentuated anxiety-avoidant personality disorder. Additionally, the twin with TTS experienced more-and also more severe-stressors involving life-threatening and dangerous situations over the life course. Discussion: These monozygous female twins with and without TTS differed in several notable aspects of their psychological functioning, psychiatric status, personality, and lifetime stressor exposure. The results thus highlight several factors, besides genetic components, that may play an important role in the pathogenesis of TTS. Looking forward, larger studies using experimental and longitudinal designs are needed to elucidate the role that psychosocial factors play in TTS. Keywords: Case report; Monozygotic twins; Psychology; Stress-induced cardiomyopathy; Takotsubo syndrome