A new agent originally introduced for localizing inflammatory lesions is Tc-99m human immunoglobulin G (HIG). Recently, focal uptake of this agent was seen in malignant lesions in a limited number of patients during inflammation imaging studies. In this prospective clinical study, the authors aimed to evaluate the uptake of Tc-99m HIG in malignant lesions. Nineteen patients with histopathologically proven malignant tumors were studied (seven had distant metastases, the primary tumor was surgically removed in two). There was no evidence of inflammation or infection in any patient. The authors imaged patients at 1, 4, and 24 hours after injection. The dose was 15-20 mCi (555-740 MBq). Focal uptake was detected in the primary tumor in six patients and in the metastases in five patients, raising some question about the specificity of Tc-99m HIG imaging for the detection of inflammation and infection.