Abstract BACKGROUND: Thyroid carcinomas represent the most frequent endocrine malignancies. Recent studies were able to distinguish malignant from benign nodules of the thyroid gland with diffusion-weighted imaging (DWI). Although this differentiation is undoubtedly helpful, presurgical discrimination between well-differentiated and undifferentiated carcinomas would be crucial to define the optimal treatment algorithm. Therefore, the aim of this study was to investigate if readout-segmented multishot echo planar DWI is able to differentiate between differentiated and undifferentiated subtypes of thyroid carcinomas. PATIENTS AND METHODS: Fourteen patients with different types of thyroid carcinomas who received preoperative DWI were included in our study. In all lesions, apparent diffusion coefficient (ADC)min, ADCmean, ADCmax, and D were estimated on the basis of region of interest measurements after coregistration with T1-weighted, postcontrast images. All tumors were resected and analyzed histopathologically. Ki-67 index, p53 synthesis, cellularity, and total and average nucleic areas were estimated using ImageJ version 1.48. RESULTS: Analysis of variance revealed a statistically significant difference in ADCmean values between differentiated and undifferentiated thyroid carcinomas ( P = .022). Spearman Rho calculation identified significant correlations between ADCmax and cell count ( r = 0.541, P = .046) as well as between ADCmax and total nuclei area ( r = 0.605, P = .022). CONCLUSION: DWI can distinguish between differentiated and undifferentiated thyroid carcinomas.