Our purpose was to determine whether the expression of cathepsin D, a proteolytic enzyme implicated in basement membrane degradation, is associated with dynamic magnetic resonance imaging (MRI) enhancement of breast lesions. Forty-five patients with 48 breast lesions underwent gadolinium-enhanced spoiled gradient recalled echo MRI followed by excisional biopsy and cathepsin D staining and semiquantitative measurement in the lesions. There was no significant difference in cathepsin D staining of 25 malignant and 23 benign breast lesions. A significant association was seen between high cathepsin D staining and positive axillary lymph nodes in invasive carcinomas. Nine of nine (100%) node-positive carcinomas had high cathepsin D, as compared to three of seven (43%) node-negative carcinomas (P = 0.02). No significant associations were observed between cathepsin D staining and MRI enhancement amplitude, rate, or washout. Cathepsin D has no effect upon MRI gadolinium enhancement of malignant and benign breast lesions but is associated with positive axillary lymph nodes in invasive carcinomas.