One hundred and seventy three women were followed-up for a median of 62 months after surgery for Stage I-III breast cancer. The concentration of cathepsin D (CD) in tumor cytosols was compared to the standard prognostic factors for the disease and related to relapse free and overall survival and type of relapse. Three groups were identified with different prognostic profile. High CD levels significantly shorten DFS in both node-negative and node-positive patients; a correlation between high cathepsin D levels and locoregional relapse should also be noted. This marker should be included in the initial evaluation of breast cancer as an indicator of invasiveness.