Fifty-five consecutively treated patients with malignant bone tumors had preoperative and postoperative chemotherapy by one oncologist. These same patients had massive bone resection and cemented endoprosthetic bone replacement by one orthopaedic oncologist. Despite 143 instances of documented fever and/or neutropenia in 45 of these 55 patients, no known deep periprosthetic infections developed in any patient during follow-up (mean, 29.4 months; median, 25 months; range, 5 months to 62 months). Broad spectrum antibiotics had been administered in at least 118 instances to these patients (intravenously in hospital, 9 times to 7 patients; intravenously at home, 38 times to 18 patients; and orally at home, 71 times to 26 patients). This study confirms the low infection rate of these massive endoprostheses, despite neutropenic and/or febrile episodes if the patient is given prophylactic broad spectrum antibiotics during the episodes. We support the continued use of massive endoprostheses for bone reconstruction in patients requiring chemotherapy.