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Ischemic limb lesions occasionally occur in neonates admitted to neonatal intensive care units. Known risk factors include the placement of arterial catheters, arterial punctures to obtain blood samples, and the use of vasoactive/vasopressor medications for hypotension. Prolonged peripheral tissue ischemia may result in serious complications, and successful management depends on early detection, proper assessment, and the institution of appropriate intervention. Currently, there is no standard approach for the management of peripheral tissue ischemia in extreme preterm infants. Topical nitroglycerine use is one of the promising options used to manage ischemic limb injuries in neonates, as demonstrated in several case reports. We report a case of digital ischemia in an extreme preterm infant with no clear risk factors except extreme prematurity, which recovered after topical nitroglycerine therapy.