OBJECTIVE To determine the correlation between alkaline phosphatase levels and bone metastases in renal cell carcinoma. METHODS The records of two cohorts, including 539 and 184 patients, with metastatic renal cell carcinoma were reviewed. In both groups, metastases were shown on magnetic resonance imaging (MRI), computed tomography (CT), or bone scan. In addition, the second cohort included data concerning pain on presentation. None of the patients in either cohort had any systemic therapy (chemotherapy or immunotherapy); many patients had undergone radical nephrectomy as the primary treatment of the cancer. All radiographic and laboratory information was obtained within a 6-week enrollment period. Normal alkaline phosphatase levels were referenced according to age and sex, resulting in an upper limit of normal of 111 to 141 U/L. RESULTS In the first cohort bone metastases were documented by MRI, CT, and/or bone scans in 164 patients. Alkaline phosphatase levels were less than or equal to 141 U/L in 118 patients (72%) and less than or equal to 111 U/L in 87 patients (53%). There were 123 patients with bone metastases who had previously undergone a nephrectomy for presumed local disease. Alkaline phosphatase levels were less than or equal to 141 U/L in 91 patients (74%) and less than or equal to 111 U/L in 70 patients (57%). In the second cohort 22 of 37 patients (59%) had little to no pain on presentation, and 19 (86%) of that group had normal alkaline phosphatase levels. CONCLUSIONS Alkaline phosphatase is an insensitive indicator of bone metastases.