OBJECTIVES: The purpose of this study was to evaluate diagnostic performance of histogram analysis using grayscale ultrasound (US) images in the diagnosis of lymphocytic thyroiditis. METHODS: Three radiologists reviewed a total of 505 US images and classified the images according to the presence/existence of lymphocytic thyroiditis. After 2 months, each reviewer repeated the process with the same 505 images in a randomly mixed order. The intraobserver and interobserver variability was analyzed with a generalized kappa value. Four histogram parameters (mean value, standard deviation, skewness, and kurtosis) were obtained, and an index was calculated from principal component analysis. Diagnostic performances were compared. RESULTS: Of 505 patients, 125 (24.8%) had lymphocytic thyroiditis, and 380 (75.2%) had normal thyroid parenchyma on pathologic analysis. The kappa value for intraobserver variance ranged from -0.002 to 0.781, and the overall kappa values for interobserver variance were 0.570 and 0.214 in the first and second tests, respectively. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for the 3 reviewers versus the principal component analysis index were 28.0% to 83.2%, 43.7% to 82.6%, 53.5% to 79.0%, 24.6% to 56.2%, and 75.2% to 88.9% versus 58.4%, 72.4%, 68.9%, 41.0%, and 84.1%. CONCLUSIONS: Histogram analysis of grayscale US images provided confirmable and quantitative information about lymphocytic thyroiditis and was comparable with performers' assessments in diagnostic performance.