Milk-alkali syndrome (MAS) is characterized by the triad of hypercalcemia, metabolic alkalosis, and acute kidney injury. Once thought to be a rare condition, there has been a resurgence of cases due to the consumption of calcium-containing supplements for osteoporosis prevention and dyspepsia in the general population. We describe the case of a female who presented with acute encephalopathy, hypercalcemia, and new-onset seizure. An extensive hypercalcemia workup and ruling out of other causes led to the diagnosis of MAS from excessive intake of calcium carbonate. Brain magnetic resonance imaging revealed signal abnormalities in the occipital and posterior parietal lobes that were indicative of posterior reversible encephalopathy syndrome. The patient’s encephalopathy resolved after treatment of her hypercalcemia with fluid resuscitation and cessation of her calcium supplements. We present our case to highlight this unusual presentation of MAS, challenges in diagnosis, and briefly discuss the pathophysiology underlying hypercalcemia-induced encephalopathy.© 2020 The Author(s).