The World Health Organization classification of tumors of the breast includes a rare variant of invasive ductal carcinoma termed pleomorphic carcinoma. This variant has marked nuclear pleomorphism (>6-fold variation in nuclear size by definition, but often>10-fold) and characteristically contains multinucleated tumor giant cells. Approximately one-third of the cases in the initial series contained a focal spindle cell metaplastic component. The tumors are reported to have an aggressive behavior, but because some contain a spindle cell metaplastic component, it is unclear whether the metaplastic component or other clinicopathologic features account for the poor clinical outcome. We identified 37 cases of pleomorphic carcinoma of the breast and evaluated the association between clinical outcome and multiple clinicopathologic features. Patients with invasive pleomorphic lobular carcinoma and those without at least a tissue biopsy before chemotherapy were excluded. Patients ranged in age from 23 to 78 years (median, 49 y). Tumor size was >5 cm in 12 cases and <5 cm in 22. A focal spindle cell component (<25% of the tumor) was present in 14 tumors (38%). Clinical follow-up was available for 36 patients (median, 17 mo). In multivariate analysis, when the 2 stage-IV patients were excluded, the presence of a spindle cell component and tumor size >5 cm were each independently associated with decreased overall survival. The actuarial 5-year overall survival for patients with and without a metaplastic spindle cell component was 38%+/-15% and 89%+/-7%, respectively. Poor clinical outcome, therefore, is associated with the subset of pleomorphic carcinomas with a spindle cell metaplastic component. As the morphologic features of pleomorphic carcinoma can be seen in primary tumors from other sites, it is important to recognize this tumor as a rare variant of invasive breast carcinoma.