The aim of this study was to investigate musculoskeletal ultrasound (MSUS) as a diagnostic modality in DISH and to explore whether it might help in elucidating its pathogenesis and events that precede the calcification/ossification process. Fifty patients with DISH and 34 patients with osteoarthritis of the lower limbs without DISH were investigated. Data regarding demographics and traditional cardiovascular risk factors were collected from all patients. An ultrasonography was performed according to the Glasgow Ultrasound Enthesitis Scoring System (GUESS) by observers who were blinded to the diagnosis or the clinical findings in the patients. The total mean GUESS score for patients with DISH was 14.12 ± 5.2 and for patients without DISH 5.32 ± 4.99 (P < 0.0001). Univariate logistic regression analysis found a strong association between the GUESS and the probability of having DISH (P < 0.0001). The area under the ROC curve (AUC) revealed that the GUESS accuracy in diagnosing DISH was 88.53% with sensitivity and specificity of 92 and 70.6%, respectively, at a cutoff value of 6.36. A stepwise logistic regression analysis of the statistically significant items in the GUESS isolated four items, and the presence of either all of them or the first three items yielded the likelihood of having DISH to be 98.8 and 90.6%, respectively. The GUESS and the stepwise logistic regression analysis of the GUESS items demonstrated a high likelihood of having DISH. MSUS might help to identify entheseal changes in DISH. Further studies are needed to confirm these results.