Breast fine-needle aspiration (FNA) is highly sensitive and specific for detecting carcinoma under most circumstances. Immunostaining for the myoepithelial cell marker p63 has been shown to be useful to separate noninvasive from invasive breast lesions in histologic examination. Its usefulness for breast FNA specimens is less certain. We performed p63 immunostains on 17 clinical samples and 29 aspirates from excised surgical specimens. One Papanicolaou-stained ThinPrep slide (Cytyc, Marlborough, MA) from each case was scored as benign, atypical, "suspicious," or positive. Cytospin (Shandon, Pittsburgh, PA) slides stained with p63 antibody were scored as to the percentage of positive single cells and percentage of positive clusters. The staining pattern of p63 was significantly different (P < .0001) between malignant and benign lesions. Based on cytology alone, the sensitivity, specificity, and positive and negative predictive values were 88%, 90%, 83%, and 93%, respectively. The application of p63 staining to specimens with a less-than-definitive diagnosis (atypical and suspicious) improved the specificity and positive and negative predictive values to 97%, 94%, and 97%, respectively. When used in conjunction with morphologic examination, p63 immunostaining may be useful to categorize cases problematic by Papanicolaou staining.