A 76-year-old man with chronic obstructive pulmonary disease and a smoking history had a 2-cm solitary pulmonary nodule that was likely to be malignant. He underwent Tc-99m-labeled somatostatin receptor-binding peptide SPECT. A computed tomographic-guided transthoracic needle biopsy performed before the SPECT was nondiagnostic. SPECT showed increased uptake of the tracer by the nodule, which was subsequently found to be adenocarcinoma by surgical resection. Differentiation of malignant from benign nodules by Tc-99m-labeled somatostatin imaging may be a reasonable approach in patients at high risk for cancer and concurrently at increased risk for complications from invasive diagnostic procedures or surgical resection.