Fine-needle aspiration (FNA) is a widely adopted procedure for the investigation of patients with mass lesions, but few studies have been published on the histologic changes resulting from the procedure. Although the effects are often minor and do not interfere with subsequent histologic diagnosis, infarction, extensive hemorrhage, and pseudomalignant changes can cause considerable problems in histologic evaluation and even lead to erroneous interpretation of benign lesions as malignancies. This article provides a comprehensive treatise on the subject, with emphasis on the thyroid, breast, lymph node, and salivary gland, the four sites on which FNA is commonly performed. The changes can be broadly classified into three groups: (a) tissue injury and repair. (b) infarction, and (c) reactive, pseudomalignant, and pseudoinvasive changes in the epithelium. Tissue injury usually takes the form of hemorrhage and hemosiderin deposit, associated with variable degrees of reparative reaction, which can occasionally be so striking that Kaposi's sarcoma or angiosarcoma is mimicked. Infarction can be focal or total and is particularly and Hurthle cell tumor. Reactive changes in the epithelium that can mimic malignancies or invasive tumors include benign implantation in or outside the fibrous capsule of benign tumors (such as thyroid follicular adenoma or mammary intraductal papilloma), epithelial displacement in benign lesions or intraductal carcinoma of the breast, reactive atypia in the benign or adenomatious epithelium (mimicking carcinoma or even angiosarcoma), and reactive epithelial or myoepithelial proliferation in salivary gland tumors. The histologic features that are helpful for recognizing the true nature of these lesions are discussed.