The differentiation of ductal and lobular carcinoma (including lobular carcinoma in situ) of the breast has important prognostic implications; thus, preoperative differentiation of these entities via fine needle aspiration could have a substantial impact on the therapeutic options offered to patients. However, well-defined, reliable light microscopic criteria do not currently exist for their distinction in cytologic preparations, particularly when the differential diagnosis of lobular versus low nuclear grade ductal carcinoma is considered. In this study we utilized a morphometric image analysis system to identify distinct nuclear features useful in the differentiation of these two entities and found that a number of significant differences do exist. Although some features (i.e., nuclear size) may be detected in traditional cytologic preparations, others may not be detected by the human observer, supporting a role for automated morphometric analysis as a useful adjunct in the distinction of lobular and low nuclear grade ductal carcinoma in fine needle aspirates of the breast.