Ki-67: a proliferative marker that may predict pulmonary metastases and mortality of primary osteosarcoma. Alterations in Ki-67 activity have been associated with tumor progression and poor outcome in cancer patients. This study was undertaken to identify the potential of this proliferative marker as a predictor of pulmonary metastases (PM) and mortality in osteosarcoma patients. In 38 patients with tissue available for immunohistochemical analysis, overexpression of Ki-67 was assessed. Chi-square and log rank tests were used to determine differences between proportions of the marker with PM and mortality and survival distributions respectively. P values equal or less than .05 were considered statistically significant. The median follow up of this case series was 28 months. Eighteen (47.4%) of 38 patients developed PM, and 17 (44%) overexpressed Ki-67. We found a high frequency of PM (15 of 17) among those cases that overexpressed Ki-67. This relationship was significant (P = .000006) when compared to the rest of the group. We also found a statistically significant correlation between patients with positive and negative Ki-67 scores and higher and lower mortality (P = .000962). These findings suggest that Ki-67 overexpression could be used as a prognostic molecular marker for the development of PM in osteosarcoma patients.