The negative predictive value of endoscopic ultrasonography fine-needle aspiration is relatively low. To achieve the improvement of the diagnostic yield, the following were proposed: a higher number of passes, the presence of the rapid on-site cytopathologist evaluation, the fanning technique, or the repetition of the fine needle biopsy. Harmonic contrast-enhanced endosonography may better identify the targeted area in the lesions by avoiding the inside necrosis and the vessels of fibrosis, so it can guide the fine-needle aspiration. Both techniques are complementary, not competitive, and they can be done in the same session. The combined technique is simple, safe, and requires only a few minutes with minimal extra costs compared to standard fine-needle aspiration. It minimally increases the diagnostic rate, and it permits the decrease of the number of passes. However, we will know its real clinical impact only in the future and whether it will be incorporated into the lesion assessment process.