Darier disease is an autosomal dominant blistering disorder linked to mutation of the endoplasmic reticulum calcium pump, SERCA2, which compromises keratinocyte adhesion and differentiation. Beyond the typical keratotic and eroded skin lesions, patients with Darier disease often present with psychiatric co-morbidities. Herein, we present a biopsy-confirmed case of Darier disease in a patient with bipolar disorder, whose cutaneous disease dramatically worsened upon initiation of lithium therapy. In consultation with the patient's psychiatrist, lithium was tapered, leading to rapid improvement in her skin. This case highlights the potential for lithium to complicate management of Darier disease and underscores the need for dermatologists to collaborate with psychiatrists to optimize both cutaneous and mental health in patients.