BACKGROUND: Prostate cancer (PC) is a complex disease that displays variable disease outcome, ranging from a relatively indolent disease to forms that result in death from the disease. One measure of disease severity is the Gleason score. Using the Gleason score as a measure of tumor aggressiveness, several independent genome scans have reported evidence of linkage. As of yet, however, no genes have been implicated. METHODS: We report an independent genome scan using the Gleason score as a quantitative trait. We genotyped 405 highly polymorphic microsatellite markers in 175 brother pairs from 103 families. RESULTS: Our strongest evidence of linkage is to 6q23 at 137 cM (D6S292, P = 0.0009). Other interesting regions (P < 0.005) were on chromosome 1p13-q21 and on chromosome 5p13-q11. CONCLUSIONS: Our results provide further evidence that tumor aggressiveness has a genetic component, and that this genetic component may be influenced by several independent genes. Copyright 2005 Wiley-Liss, Inc.