Tumor lysis syndrome (TLS) is the destruction of tumor cells, causing the release of intracellular contents, including but not limited to uric acid, phosphate, and potassium. This can manifest with significant physiologic abnormalities, such as life-threatening acute kidney injury. Although TLS is usually caused by the initiation of cytotoxic chemotherapy, it may also occur spontaneously, particularly in high-grade malignancies with high tumor burden and/or rapid cell turnover. Here, we present a case of spontaneous TLS in a patient with early-phase pancreatic cancer diagnosis and possible signs of metastasis. Additionally, we provide a comprehensive review of the current literature regarding this phenomenon. In the present case, our patient was stabilized using aggressive intravenous hydration and pharmacotherapy. This case report adds to the slowly growing literature surrounding the diagnosis and management of spontaneous TLS in pancreatic adenocarcinomas.