Reduction mammaplasty is the fifth most common reconstructive surgical procedure in the United States. The incidence of invasive breast cancer in breast reduction specimens is between 0.06 and 0.4 percent. However, the incidence of atypical hyperplasia and other precancerous lesions is not well described. The authors conducted a single-center retrospective chart review examining the incidence of benign and precancerous lesions in breast reduction specimens over a 5-year period. Of the 562 patients who underwent reduction mammaplasty, 52.7 percent had nonproliferative or proliferative breast lesions. Twenty-five patients (4.4 percent) had a specimen containing atypical ductal or lobular hyperplasia. Six patients (1.1 percent) had ductal carcinoma in situ and four patients (0.7 percent) had lobular carcinoma in situ. No occult invasive breast cancer was identified in the breast reduction specimens, but one patient with ductal carcinoma in situ was found to have invasive breast cancer on completion mastectomy (0.2 percent). This study demonstrates the importance of systematic analysis of breast reduction specimens to help identify and guide the management of patients with increased risk of breast cancer following reduction mammaplasty.