Studies evaluating the biological behavior of primary squamous cell carcinoma (SCC) of the breast have yielded inconsistent results, perhaps in part because most studies have not taken into consideration specific histologic subtypes. We identified 21 cases of primary SCC of the breast diagnosed between the years 1985 and 2010 and analyzed the association between particular histologic features and disease outcome. Most tumors (17/21) were moderately or poorly differentiated, and most had a high nuclear grade (15/21). Five-year locoregional recurrence-free survival (LRRFS) for all patients was 54%±12%, and 5-year overall survival (OS) was 51%±13%. The only statistically significant feature associated with LRRFS was the presence of a spindle cell component in the tumor. Patients with >10% spindle cell component had decreased LRRFS (log rank; P=0.006). The only statistically significant features associated with OS were patient age and tumor keratinization. Patients more than 60 years of age had decreased OS (log rank; P=0.035), and patients with tumors having at least focal keratinization had improved OS (log rank; P=0.027). Lymph node status, mitotic rate, tumor necrosis, cystic degeneration, clear cell change, and the presence of a pleomorphic component or associated ductal carcinoma in situ were not associated with either LRRFS or OS. In summary, primary SCC of the breast tends to be aggressive, particularly in patients more than 60 years of age and those with tumors having >10% spindle cell component. The presence of at least focal keratinization, however, is associated with significantly improved OS.