A case of chronic osteomyelitis complicated by the development of squamous cell carcinoma in the sinus tract is described. This complication was itself associated with the development of humoral hypercalcemia of malignancy, a phenomenon not previously described in this context. Common misconceptions relating to the interpretation of serum parathyroid hormone levels led to the misdiagnosis of hyperparathyroidism and parathyroid exploration. Forced saline diuresis, mithramycin and oral phosphate supplements were not able to provide long-term control of the hypercalcemia but the patient was subsequently managed successfully with intravenous (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) and resection of the causative tumour.