Tumor lysis syndrome (TLS) consists of acute hyperuricemic nephropathy, hyperphosphatemia, hypocalcemia, hyperkalemia, and increased serum creatinine. It can be part of the disease presentation, especially in aggressive hematologic malignancies, or a part of the chemotherapy response. There are relatively few reports of TLS in solid tumors. Herein, we present 3 cases-1 small-cell lung cancer case and 2 breast cancer cases-that developed signs consistent with TLS upon initiation of treatment. Identified risk factors include disease bulk, aggressive growth, hepatic involvement, and pretreatment laboratory abnormalities such as elevated lactate dehydrogenase, uric acid, and creatinine. All 3 patients responded to hydration and allopurinol. One patient received rasburicase. Although the reported number of TLS cases associated with solid tumors is small, it may be that it is underdiagnosed or unsuspected in most situations. The purpose of this report is to alert clinicians to the possibility of TLS, even in solid tumors, so they can preemptively manage it.