Darier disease is a rare autosomal dominant disorder that results from a mutation in the gene coding for the endoplasmic reticulum membrane calcium pump Ca2+-ATPase type 2 (SERCA2), leading to compromised intercellular adhesion. Patients typically present in the first two decades of life with keratotic, greasy papules in a seborrheic distribution. Segmental Darier disease is a variant with localized disease that follows Blaschko lines. Treatment options include topical and systemic agents including corticosteroids, retinoids, and antibiotics. We present a 67-year-old woman who came to our clinic with segmental Darier disease recalcitrant to topical therapy. Owing to cost and side effect profile, the patient declined treatment with oral retinoids. Doxycycline 100mg daily was started with significant improvement. Tetracyclines both chelate and assist calcium to cross membranes. This mechanism may correct the cellular calcium imbalance present in Darier disease. In addition, tetracyclines have been shown to inhibit metalloproteinase 9, an important part of Darier disease pathogenesis. Owing to its favorable side effect profile, further investigation is warranted to establish doxycycline as a more widely utilized treatment option for Darier disease.