Patients who present with facial pigmentation can be a diagnostic challenge. The goal of this study was to discuss the diagnosis and management of imipramine-induced facial pigmentation. We describe a patient with facial pigmentation of 26 years' duration that was associated with imipramine treatment for depression. We discuss light and election microscopic findings and review 11 previously reported cases of imipramine-induced skin pigmentation. Examination showed blue-gray facial pigmentation. Light microscopy showed perivascular pigment granule deposits in the upper dermis that stained positively with Fontana-Masson stain and negatively with Prussian blue stain. Electron microscopy showed electron-dense bodies within histiocytes without clearly identifiable melanin granules, consistent with drug-induced pigmentation. Six weeks after switching to sertraline the patient reported a slight improvement of her cutaneous pigmentation. Imipramine is a rare cause of gray-blue facial pigmentation. Light microscopy consistently shows granular dermal deposits that stain positively with Fontana-Masson stain but negatively with iron stain.