Indium-111-labeled autologous leukocyte studies in general carry a high sensitivity, specificity, and accuracy for the investigation of infections and abscesses. However, past studies have described sporadic cases in which 111In leukocytes localized in tumors. Our experience using 111In leukocytes for the investigation of fever of unknown origin in cancer patients, however, indicates a relatively high incidence of 111In leukocyte localization in noninfected neoplasms. Out of the 61 patients studied for fever of unknown origin, 21 patients (34%) manifested abnormal localization of 111In leukocytes in neoplasms without clinical evidence of infection. These included patients with abnormal localization in: (a) lymph nodes, (b) soft-tissue tumors, and (c) bone neoplasms. The tumors included both primary and secondary lesions, and hematologic as well as solid tumors. The mechanism of 111In leukocyte localization in tumors is still not completely explained. Interpretations of 111In leukocyte studies in cancer patients with fever should take into consideration the possibility that localization may occur in neoplastic tissue per se and does not always indicate the presence of infection.