Introduction: Large rectal lesions can conceal submucosal invasion and cancer nodules. Despite the increasing diffusion of high-definition endoscopes and the importance of an accurate morphological evaluation, a complete assessment in this setting can be challenging. Endoscopic ultrasound (EUS) plays an established role in the locoregional staging of rectal cancer, although this technique has a tendency toward the over-estimation of the loco-regional (T) staging. However, there are still few data on contrast-enhanced endoscopic ultrasound (CH-EUS), especially if this ancillary technique may increase the accuracy for predicting invasive nodules among large rectal lesions. Material and Methods: Consecutive large (≥20 mm) superficial rectal lesions with high-definition endoscopy, characterized by focal areas suggestive for invasive cancer/2B type according to JNET classification, were considered for additional standardized evaluation via CH-EUS with Sonovue ©. Results: From 2020 to 2023, we evaluated 12 consecutive superficial rectal lesions with sizes ranging from 20 to 180 mm. This evaluation provided additional elements to support the therapeutic decision made. Lesions were treated with surgical (3/12) or endoscopic treatment (9/12) according to their morphology and CH-EUS evaluation. Conclusion: Contrast-enhanced endoscopic ultrasound can provide an additional evaluation for large and difficult-to-classify rectal lesions. In our experience, CH-EUS staging corresponded to the final pathological stages in 9/12 (75%) lesions, improving the distinction between T1 and T2 lesions. Larger prospective studies and randomized trials should be conducted to support and standardize this approach.